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1. Associations between general and specific mental health conditions in young adulthood and cardiometabolic complications in middle adulthood : A 40-year longitudinal familial coaggregation study of 672 823 Swedish individuals

Author: Chen, C., Chang, Z., Kuja-Halkola, R., D'Onofrio, B. M., Larsson, Henrik, Andell, P., Lichtenstein, P., Pettersson, E., Chen, C., Chang, Z., Kuja-Halkola, R., D'Onofrio, B. M., Larsson, Henrik, Andell, P., Lichtenstein, P., and Pettersson, E.
Abstract: Introduction: Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability toward psychopathology or confounded by unmeasured familial factors. Objectives: To examine whether the associations between psychiatric diagnoses and increased risk of cardiometabolic complications are attributable to a general liability toward psychopathology, or confounded by unmeasured familial factors. Methods: We conducted a cohort study in Sweden and identified all individuals and their siblings born in Sweden 1955-1962 with follow-up through 2013. After excluding individuals who died or emigrated before 1987, the final sample consisted 672 823 individuals. We extracted ICD-coded diagnoses (recorded 1973-1987) for ten psychiatric conditions and criminal convictions when participants were aged 18-25 years, and ICD-coded diagnoses (recorded 1987-2013) for five cardiometabolic complications (obesity, hypertensive diseases, hyperlipidemia, type 2 diabetes mellitus, and cardiovascular diseases) when the participants were 51-58 years old. Logistic regression models were used to estimate the bivariate associations between psychiatric conditions or criminal convictions and cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the psychiatric conditions and criminal convictions. We then regressed the cardiometabolic complications on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs. Results: Each psychiatric conditions significantly increased the risk of cardiometabolic complications; however, most of these associations were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small asso, DOI not working: 10.1192/j.eurpsy.2023.230
Published: 2023

2. Chronic pain conditions and risk of suicidal behavior : a 10-year longitudinal co-twin control study

Author: Chen, C., Pettersson, E., Summit, A. G., Boersma, Katja, Chang, Z., Kuja-Halkola, R., Lichtenstein, P, Quinn, P D, Chen, C., Pettersson, E., Summit, A. G., Boersma, Katja, Chang, Z., Kuja-Halkola, R., Lichtenstein, P, and Quinn, P D
Abstract: BACKGROUND: Understanding the relationship between chronic pain conditions and suicidal behavior-suicide attempt, other intentional self-harm, and death by suicide-is imperative for suicide prevention efforts. Although chronic pain conditions are associated with suicidal behaviors, these associations might be attributed to unmeasured confounding or mediated via pain comorbidity. METHODS: We linked a population-based Swedish twin study (N=17,148 twins) with 10 years of longitudinal, nationwide records of suicidal behavior from health and mortality registers through 2016. To investigate whether pain comorbidity versus specific pain conditions were more important for later suicidal behavior, we modeled a general factor of pain and two independent specific pain factors (measuring pain-related somatic symptoms and neck-shoulder pain, respectively) based on 9 self-reported chronic pain conditions. To examine whether the pain-suicidal behavior associations were attributable to familial confounding, we applied a co-twin control model. RESULTS: Individuals scoring one standard deviation above the mean on the general pain factor had a 51% higher risk of experiencing suicidal behavior (odds ratio (OR), 1.51; 95% confidence interval (CI), 1.34-1.72). The specific factor of somatic pain was also associated with increased risk for suicidal behavior (OR, 1.80; 95% CI, 1.45-2.22]). However, after adjustment for familial confounding, the associations were greatly attenuated and not statistically significant within monozygotic twin pairs (general pain factor OR, 0.89; 95% CI, 0.59-1.33; somatic pain factor OR, 1.02; 95% CI, 0.49-2.11) CONCLUSION: Clinicians might benefit from measuring not only specific types of pain, but also pain comorbidity; however, treating pain might not necessarily reduce future suicidal behavior, as the associations appeared attributable to familial confounding., Funding agencies:American Foundation for Suicide Prevention SRG-0-133-19China Scholarship Council CSC201806360008
Published: 2023
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3. Associations Between Psychiatric Polygenic Risk Scores and General and Specific Psychopathology Symptoms in Childhood and Adolescence : A Co-twin Control Study

Author: Chen, C., Lu, Y., Lundström, S., Larsson, Henrik, Lichtenstein, P., Pettersson, E., Chen, C., Lu, Y., Lundström, S., Larsson, Henrik, Lichtenstein, P., and Pettersson, E.
Abstract: Funding agency:China Scholarship Council CSC201806360008
Published: 2021

4. Voices of children with intellectual disabilities on participation in daily activities

Author: Huus, Karina, Morwane, R, Ramaahlo, M, Balton, S, Pettersson, E, Gimbler Berglund, Ingalill, Dada, S, Huus, Karina, Morwane, R, Ramaahlo, M, Balton, S, Pettersson, E, Gimbler Berglund, Ingalill, and Dada, S
Abstract: Background: Participation in daily activities is expressed as a human right. Full participation of children with disabilities in daily activities creates optimal opportunities for learning and development. Previous studies have focused primarily on proxy ratings of participation of children with intellectual disabilities in daily activities. However, little is known about how the children rate barriers and facilitators to their participation in everyday activities. Objectives: To identify barriers to and facilitators for everyday activities as experienced by children with intellectual disabilities from low- and middle-income countries and high-income countries. The research questions were as follows: 'what barriers to participation do children with disabilities experience in everyday activities?' and 'what facilitators to participation do children with disabilities experience in everyday activities?' Method: A qualitative content analyses was used in this study, and individual interviews were conducted with 49 children with intellectual disabilities. The interviews were performed using pictures. The children also selected the most important activities and described in their own words the facilitators and barriers relevant to being able to perform the activities. Results: The most important activities were organised leisure activities, formal learning at school, taking care of other family members and family mealtimes. Self-reported barriers identified were personal functioning, social exclusion and lack of resources. The identified facilitators included satisfaction, personal capability, being included and having access to resources. Conclusion: These findings provide important knowledge about the factors to consider in the development of interventions, aimed at improving the participation of children with intellectual disabilities.
Published: 2021
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5. The general factor of psychopathology : a comparison with the general factor of intelligence with respect to magnitude and predictive validity

Author: Pettersson, E., Larsson, Henrik, D'Onofrio, B. M., Bölte, S., Lichtenstein, P., Pettersson, E., Larsson, Henrik, D'Onofrio, B. M., Bölte, S., and Lichtenstein, P.
Abstract: In recent years, there has been a surge of interest in the general factor of psychopathology (“p”), which is intended to summarize broad psychiatric comorbidity into a single index. In this study, rather than attempting to validate this model using statistical techniques, we compared the magnitude (as indicated by the variance explained in the respective indicators) and the predictive validity of the “p” factor with those of the general factor of intelligence (“g”). To compare the magnitude, for “g”, we analyzed fifteen Wechsler Adult Intelligence Scale subtests (N=1,200). For “p”, we analyzed fourteen psychiatric diagnoses in Swedish adults (N=909,699), eight self- and parent-rated psychopathology scales in Swedish adolescents (N=2,069), and sixteen parent-rated psychopathology scales in Swedish children (N=14,589). To compare the predictive validity, we analyzed Swedish male military conscripts (N=414,595, mean age: 18.3 years) with measures on both “g” and “p” (derived from eight psychiatric diagnoses). We then examined their unique associations with three intelligence-related outcomes (annual income, highest education, and university entrance exam scores), and sixteen adverse outcomes (e.g., suicidal behavior, psychotropic medication prescription, and criminality) retrieved from registers (mean age at follow-up = 29.2 years). Results indicated that the magnitudes of “g” and “p” were very similar. Controlling for “p”, “g” significantly predicted later education (standardized beta, β=0.38, SE=0.01) and university entrance exam scores (β=0.48, SE=0.01). Controlling for “g”, “p” significantly predicted all adverse outcomes (mean β=0.32; range: 0.15 to 0.47). These findings support the notion that psychopathology indicators can be combined into a single score, similar to how intelligence subtests are combined into a general intelligence score. This “p” score might supplement specific diagnoses when formulating a management plan and predicting prognosis., Funding Agency:Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM) 340-2013-5867
Published: 2020
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6. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author: Glanville, KP, Coleman, JR, Hanscombe, KB, Euesden, J, Choi, SW, Purves, KL, Breen, G, Air, TM, Andlauer, TFM, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Buttenschon, HN, Colodro-Conde, L, Dannlowski, U, Direk, N, Dunn, EC, Forstner, AJ, de Geus, EJC, Grabe, HJ, Hamilton, SP, Jones, I, Jones, LA, Knowles, JA, Kutalik, Z, Levinson, DF, Lewis, G, Lind, PA, Lucae, S, Magnusson, PK, McGuffin, P, McIntosh, AM, Milaneschi, Y, Mors, O, Mostafavi, S, Mueller-Myhsok, B, Pedersen, NL, Penninx, BWJH, Potash, JB, Preisig, M, Ripke, S, Shi, J, Shyn, S, Smoller, JW, Streit, F, Sullivan, PF, Tiemeier, H, Uher, R, Van der Auwera, S, Weissman, MM, O'Reilly, PF, Lewis, CM, Wray, NR, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Bryois, J, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Dolan, C, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jorgenson, E, Kohane, IS, Kraft, J, Kretzschmar, WW, Li, Y, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milani, L, Mondimore, FM, Montgomery, GW, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Cichon, S, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Li, QS, Madden, PAF, Martin, NG, Metspalu, A, Mortensen, PB, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Perlis, RH, Porteous, DJ, Rietschel, M, Schaefer, C, Schulze, TG, Stefansson, K, Voelzke, H, Werge, T, Borglum, AD, Glanville, KP, Coleman, JR, Hanscombe, KB, Euesden, J, Choi, SW, Purves, KL, Breen, G, Air, TM, Andlauer, TFM, Baune, BT, Binder, EB, Blackwood, DHR, Boomsma, D, Buttenschon, HN, Colodro-Conde, L, Dannlowski, U, Direk, N, Dunn, EC, Forstner, AJ, de Geus, EJC, Grabe, HJ, Hamilton, SP, Jones, I, Jones, LA, Knowles, JA, Kutalik, Z, Levinson, DF, Lewis, G, Lind, PA, Lucae, S, Magnusson, PK, McGuffin, P, McIntosh, AM, Milaneschi, Y, Mors, O, Mostafavi, S, Mueller-Myhsok, B, Pedersen, NL, Penninx, BWJH, Potash, JB, Preisig, M, Ripke, S, Shi, J, Shyn, S, Smoller, JW, Streit, F, Sullivan, PF, Tiemeier, H, Uher, R, Van der Auwera, S, Weissman, MM, O'Reilly, PF, Lewis, CM, Wray, NR, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Bryois, J, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Dolan, C, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jorgenson, E, Kohane, IS, Kraft, J, Kretzschmar, WW, Li, Y, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milani, L, Mondimore, FM, Montgomery, GW, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Cichon, S, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Li, QS, Madden, PAF, Martin, NG, Metspalu, A, Mortensen, PB, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Perlis, RH, Porteous, DJ, Rietschel, M, Schaefer, C, Schulze, TG, Stefansson, K, Voelzke, H, Werge, T, and Borglum, AD
Abstract: BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.
Published: 2020

7. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Author: Coleman, JRI, Peyrot, WJ, Purves, KL, Davis, KAS, Rayner, C, Choi, SW, Hubel, C, Gaspar, HA, Kan, C, Van der Auwera, S, Adams, MJ, Lyall, DM, Choi, KW, Dunn, EC, Vassos, E, Danese, A, Maughan, B, Grabe, HJ, Lewis, CM, O'Reilly, PF, McIntosh, AM, Smith, DJ, Wray, NR, Hotopf, M, Eley, TC, Breen, G, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Volzke, H, Weissman, MM, Werge, T, Levinson, DF, Borglum, AD, Sullivan, PF, Coleman, JRI, Peyrot, WJ, Purves, KL, Davis, KAS, Rayner, C, Choi, SW, Hubel, C, Gaspar, HA, Kan, C, Van der Auwera, S, Adams, MJ, Lyall, DM, Choi, KW, Dunn, EC, Vassos, E, Danese, A, Maughan, B, Grabe, HJ, Lewis, CM, O'Reilly, PF, McIntosh, AM, Smith, DJ, Wray, NR, Hotopf, M, Eley, TC, Breen, G, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Howard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Volzke, H, Weissman, MM, Werge, T, Levinson, DF, Borglum, AD, and Sullivan, PF
Abstract: Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.
Published: 2020

8. Genetic and environmental contribution to the overlap between ADHD and ASD trait dimensions in young adults: a twin study.

Author: Ghirardi, L., Pettersson, E., Taylor, M.J., Freitag, C.M., Franke, B., Asherson, P., Larsson, H., Kuja-Halkola, R., Ghirardi, L., Pettersson, E., Taylor, M.J., Freitag, C.M., Franke, B., Asherson, P., Larsson, H., and Kuja-Halkola, R.
Abstract: 01 juli 2019, Contains fulltext : 207153.pdf (publisher's version ) (Open Access), BACKGROUND: Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults. METHODS: We studied 6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components. RESULTS: At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31-0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI 0.21-0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23-0.43). CONCLUSIONS: We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.
Published: 2019

9. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Author: Andlauer, T.F.M. (Till F. M.), Guzman-Parra, J. (Jose), Streit, F. (Fabian), Strohmaier, J. (Jana), González, M.J. (Maria José), Gil Flores, S. (Susana), Cabaleiro Fabeiro, F.J. (Francisco J.), del Río Noriega, F. (Francisco), Perez, F.P. (Fermin Perez), Haro González, J. (Jesus), Orozco Diaz, G. (Guillermo), Diego, Y. (Yolanda) de, Moreno-Küstner, B. (Berta), Auburger, G. (Georg), Degenhardt, F. (Franziska), Heilmann-Heimbach, S. (Stefanie), Herms, S. (Stefan), Hoffmann, P. (Per), Frank, J. (Josef), Foo, J.C. (Jerome C.), Treutlein, J. (Jens), Witt, S.H. (Stephanie H), Cichon, S. (Sven), Kogevinas, M. (Manolis), Stahl, E.A. (Eli A), Breen, G. (Gerome), Forstner, A.J. (Andreas J), McQuillin, A. (Andrew), Ripke, S. (Stephan), Trubetskoy, V. (Vassily), Mattheisen, M. (Manuel), Wang, Y. (Yunpeng), Coleman, J.R.I. (Jonathan R I), Gaspar, H.A. (Héléna A), Leeuw, C. (Christiaan) de, Steinberg, S. (Stacy), Pavlides, J.M.W. (Jennifer M Whitehead), Trzaskowski, M. (Maciej), Pers, T.H. (Tune H), Holmans, P.A. (Peter A.), Abbott, L. (Liam), Agerbo, E. (Esben), Akil, H. (Huda), Albani, D. (Diego), Alliey-Rodriguez, N. (Ney), Als, T.D. (Thomas D), Anjorin, A. (Adebayo), Antilla, V. (Verneri), Awasthi, S. (Swapnil), Badner, J.A. (Judith A), Bækvad-Hansen, M. (Marie), Barchas, J.D. (Jack D), Bass, N. (Nicholas), Bauer, M. (Michael), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Pedersen, C.B. (C.), Bøen, E. (Erlend), Boks, M.P.M. (Marco), Boocock, J. (James), Budde, M. (Monika), Bunney, W.E. (William E), Burmeister, M., Bybjerg-Grauholm, J. (Jonas), Byerley, W.F. (William F), Casas, M. (Miquel), Cerrato, F. (Felecia), Cervantes, P. (Pablo), Chambert, K. (Kimberly), Charney, A.W. (Alexander W), Chen, D. (Danfeng), Churchhouse, C. (Claire), Clarke, T.-K. (Toni-Kim), Coryell, W.H. (William H), Craig, D.W. (David W), Cruceanu, C. (Cristiana), Czerski, P.M., Dale, A.M. (Anders), de Jong, S. (Simone), Del-Favero, J. (Jurgen), DePaulo, J.R. (J Raymond), Djurovic, S. (Srdjan), Dobbyn, A.L. (Amanda L), Dumont, A. (Ashley), Elvsåshagen, T. (Torbjørn), Escott-Price, V. (Valentina), Fan, C.C. (Chun Chieh), Fischer, S.B. (Sascha B), Flickinger, M. (Matthew), Foroud, T.M. (Tatiana M), Forty, L. (Liz), Fraser, C. (Christine), Luben, R.N. (Robert), Frisén, L. (Louise), Gade, K. (Katrin), Gage, D. (Diane), Garnham, J. (Julie), Giambartolomei, C. (Claudia), Pedersen, M.G. (Marianne Giørtz), Goldstein, J.I. (Jacqueline), Gordon, S.D. (Scott D), Gordon-Smith, K. (Katherine), Green, E.K. (Elaine K), Green, M.J. (Melissa J), Greenwood, T.A. (Tiffany A), Grove, J. (Jakob), Guan, W. (Weihua), Parra, J.G. (José Guzman), Hamshere, M.L. (Marian), Hautzinger, M. (Martin), Heilbronner, U. (Urs), Hipolito, M. (Maria), Holland, D. (Dominic), Huckins, L. (Laura), Jamain, S. (Stéphane), Johnson, J.S. (Jessica S), Juréus, A. (Anders), Kandaswamy, R. (Radhika), Karlsson, R. (Robert), Kennedy, J.L. (James L), Kittel-Schneider, S. (Sarah), Knowles, J.A. (James A), Koller, A.C. (Anna C), Kupka, R.W. (Ralph ), Lavebratt, C. (Catharina), Lawrence, J. (Jacob), Lawson, W.B. (William B), Leber, I. (Isabelle), Lee, P.H. (Phil H), Levy, S.E. (Shawn E), Li, J.Z. (Jun Z), Liu, C. (Chunyu), Lucae, S. (Susanne), Maaser, A. (Anna), Macintyre, D.J. (Donald J), Mahon, P.B. (Pamela B), Maier, W. (Wolfgang), Martinsson, L. (Lina), McCarroll, S.A. (Steve), McGuffin, P. (Peter), Mcinnis, M.G. (Melvin G), McKay, J.D. (James D), Medeiros, H. (Helena), Medland, S.E. (Sarah E), Meng, F. (Fan), Milani, L. (Lili), Montgomery, G.W. (Grant W), Morris, D.W. (Derek W), Mühleisen, T.W. (Thomas W), Mullins, N. (Niamh), Nguyen, H. (Hoang), Nievergelt, C.M. (Caroline M), Adolfsson, A.N. (Annelie Nordin), Nwulia, E.A. (Evaristus A), O’Donovan, C. (Claire), Loohuis, L.M.O. (Loes M Olde), Ori, A.P.S. (Anil P S), Oruc, L. (Lilijana), Ösby, U. (Urban), Perlis, R.H. (Roy H), Perry, A. (Amy), Pfennig, A. (Andrea), Potash, J.B. (James B), Purcell, S.M. (Shaun M), Regeer, E.J. (Eline Janet), Reif, A. (Andreas), Reinbold, C.S. (Céline S), Rice, J.P. (John), Richards, A. (Alex), Rivas, F. (Fabio), Rivera, M. (Margarita), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Ryu, J. (Julie), Sánchez-Mora, C. (Cristina), Schatzberg, A.F. (Alan F), Scheftner, W.A. (William A), Schork, N.J. (Nicholas), Weickert, C.S. (Cynthia Shannon), Shehktman, T. (Tatyana), Shilling, P.D. (Paul D), Sigurdsson, E. (Engilbert), Slaney, C. (Claire), Smeland, O.B. (Olav B), Sobell, J.L. (Janet L), Hansen, C.S. (Christine Søholm), Spijker, A.T. (Anne T), Clair, D.S., Steffens, M. (Michael), Strauss, J.S. (John S), Szelinger, S. (Szabolcs), Thompson, R.C. (Robert C), EThorgeirsson, T. (Thorgeir), Vedde, H. (Helmut), Wang, W. (Weiqing), Watson, S.J. (Stanley J), Weickert, T.W. (Thomas W), Xi, S. (Simon), Xu, W. (Wei), Young, A.H. (Allan H), Zandi, P.P. (Peter P), Zhang, P. (Ping), Zöllner, S. (Sebastian), Adolfsson, R., Agartz, I. (Ingrid), Alda, M. (Martin), Backlund, L. (Lena), Baune, B.T. (Bernhard T), Bellivier, F. (Frank), Berrettini, W. (Wade), Biernacka, J.M. (Joanna M), Blackwood, D.H.R. (Douglas), Boehnke, M. (Michael), Børglum, A.D. (Anders D), Corvin, A. (Aiden), Craddock, N. (Nicholas), Daly, M.J. (Mark), Dannlowski, U. (Udo), Esko, T. (Tõnu), Etain, B. (Bruno), Frye, M.A. (Mark A), Fullerton, J.M. (Janice M), Gershon, E.S. (Elliot S), Gill, M. (Michael), Goes, F. (Fernando), Grigoroiu-Serbanescu, M. (Maria), Hauser, J. (J.), Hougaard, D.M. (David M), Hultman, C.M. (Christina), Jones, I. (Ian), Jones, L.A. (Lisa A), Kahn, R. (René), Kirov, G. (George), Landén, M. (Mikael), Leboyer, M. (Marion), Lewis, C.M. (Cathryn), Li, Q.S. (Qingqin S), Lissowska, J. (Jolanta), Martin, N.G. (Nicholas), Mayoral, F. (Fermin), McElroy, S.L. (Susan L), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Melle, I. (Ingrid), Metspalu, A. (Andres), Mitchell, P.B. (Philip B), Morken, G. (Gunnar), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (Bertram), Myers, R.H. (Richard), Neale, B.M. (Benjamin), Nimgaonkar, V. (Vishwajit), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C), Oedegaard, K.J. (Ketil J), Owen, M.J. (Michael J), Paciga, S.A. (Sara A), Pato, C. (Carlos), Posthuma, D. (Danielle), Ramos-Quiroga, J.A. (Josep Antoni), Ribasés, M. (Marta), Rietschel, M. (Marcella), Rouleau, G.A. (Guy A), Schalling, M. (Martin), Schofield, P.R. (Peter R), Schulze, T.G. (Thomas G), Serretti, A. (Alessandro), Smoller, J.W., Stefansson, H. (Hreinn), Zwart, J-A. (John-Anker), Stordal, E. (Eystein), Sullivan, P.F. (Patrick F), Turecki, G. (Gustavo), Vaaler, A.E. (Arne E), Vieta, E. (Eduard), Vincent, J.B. (John B), Werge, T.M. (Thomas), Nurnberger, J.I. (John I), Wray, N.R. (Naomi), Florio, A.D. (Arianna Di), Edenberg, H.J. (Howard), Ophoff, R.A. (Roel), Scott, L.J. (Laura J), Andreassen, O.A. (Ole), Kelsoe, J.R. (John), Sklar, P. (Pamela), Wray, N.R. (Naomi R), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J), Air, T.M. (Tracy M), Bacanu, S.A. (Silviu), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B), Binder, E.B. (Elisabeth), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E), Davies, G. (Gail), Deary, I.J. (Ian J), Degenhardt, F., Derks, E.M. (Eske M), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K), Foo, J.C. (Jerome C), Goes, F.S. (Fernando S), Gordon, S.D. (Scott D.), Hall, L.S. (Lynsey S), Hansen, T.F. (Thomas F), Hickie, I.B. (Ian), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M), Ising, M. (Marcus), Jansen, R. (Rick), Jones, I., Jones, L. (Louisa), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), MacIntyre, D.J. (Donald J), MacKinnon, D.F. (Dean F), Maier, R.M. (Robert M), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Mcguffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel M), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Mondimore, F.M. (Francis M), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (Carsten Bøcker), Peterson, R.E. (Roseann E), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Quiroz, J.A. (Jorge A), Qvist, P. (Per), Rice, J.P. (John P), Riley, B.P. (Brien P.), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C), Shen, L. (Li), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sinnamon, G.C.B. (Grant C B), Smith, A.V. (Davey), Smith, D.J. (Daniel J), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A), Thorgeirsson, T.E. (Thorgeir E), Traylor, M. (Matthew), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M), Viktorin, A. (Alexander), Visscher, P.M. (Peter M), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Wu, Y. (Yang), Xi, H.S. (Hualin S), Yang, J. (Joanna), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Domenici, E. (Enrico), Domschke, K. (Katharina), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas G), McIntosh, A.M. (Andrew M), Mors, O., Müller-Myhsok, B. (B.), Nöthen, M.M. (Markus M), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Porteous, D.J. (David J.), Preisig, M. (Martin), Schaefer, C. (Catherine), Smoller, J.W. (Jordan W), Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn M), Levinson, D.F. (Douglas F.), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick), Mayoral, F. (Fermín), Muller-Myhsok, B. (B.), Forstner, A.J. (Andreas J.), Nöthen, M.M. (Markus M.), Andlauer, T.F.M. (Till F. M.), Guzman-Parra, J. (Jose), Streit, F. (Fabian), Strohmaier, J. (Jana), González, M.J. (Maria José), Gil Flores, S. (Susana), Cabaleiro Fabeiro, F.J. (Francisco J.), del Río Noriega, F. (Francisco), Perez, F.P. (Fermin Perez), Haro González, J. (Jesus), Orozco Diaz, G. (Guillermo), Diego, Y. (Yolanda) de, Moreno-Küstner, B. (Berta), Auburger, G. (Georg), Degenhardt, F. (Franziska), Heilmann-Heimbach, S. (Stefanie), Herms, S. (Stefan), Hoffmann, P. (Per), Frank, J. (Josef), Foo, J.C. (Jerome C.), Treutlein, J. (Jens), Witt, S.H. (Stephanie H), Cichon, S. (Sven), Kogevinas, M. (Manolis), Stahl, E.A. (Eli A), Breen, G. (Gerome), Forstner, A.J. (Andreas J), McQuillin, A. (Andrew), Ripke, S. (Stephan), Trubetskoy, V. (Vassily), Mattheisen, M. (Manuel), Wang, Y. (Yunpeng), Coleman, J.R.I. (Jonathan R I), Gaspar, H.A. (Héléna A), Leeuw, C. (Christiaan) de, Steinberg, S. (Stacy), Pavlides, J.M.W. (Jennifer M Whitehead), Trzaskowski, M. (Maciej), Pers, T.H. (Tune H), Holmans, P.A. (Peter A.), Abbott, L. (Liam), Agerbo, E. (Esben), Akil, H. (Huda), Albani, D. (Diego), Alliey-Rodriguez, N. (Ney), Als, T.D. (Thomas D), Anjorin, A. (Adebayo), Antilla, V. (Verneri), Awasthi, S. (Swapnil), Badner, J.A. (Judith A), Bækvad-Hansen, M. (Marie), Barchas, J.D. (Jack D), Bass, N. (Nicholas), Bauer, M. (Michael), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Pedersen, C.B. (C.), Bøen, E. (Erlend), Boks, M.P.M. (Marco), Boocock, J. (James), Budde, M. (Monika), Bunney, W.E. (William E), Burmeister, M., Bybjerg-Grauholm, J. (Jonas), Byerley, W.F. (William F), Casas, M. (Miquel), Cerrato, F. (Felecia), Cervantes, P. (Pablo), Chambert, K. (Kimberly), Charney, A.W. (Alexander W), Chen, D. (Danfeng), Churchhouse, C. (Claire), Clarke, T.-K. (Toni-Kim), Coryell, W.H. (William H), Craig, D.W. (David W), Cruceanu, C. (Cristiana), Czerski, P.M., Dale, A.M. (Anders), de Jong, S. (Simone), Del-Favero, J. (Jurgen), DePaulo, J.R. (J Raymond), Djurovic, S. (Srdjan), Dobbyn, A.L. (Amanda L), Dumont, A. (Ashley), Elvsåshagen, T. (Torbjørn), Escott-Price, V. (Valentina), Fan, C.C. (Chun Chieh), Fischer, S.B. (Sascha B), Flickinger, M. (Matthew), Foroud, T.M. (Tatiana M), Forty, L. (Liz), Fraser, C. (Christine), Luben, R.N. (Robert), Frisén, L. (Louise), Gade, K. (Katrin), Gage, D. (Diane), Garnham, J. (Julie), Giambartolomei, C. (Claudia), Pedersen, M.G. (Marianne Giørtz), Goldstein, J.I. (Jacqueline), Gordon, S.D. (Scott D), Gordon-Smith, K. (Katherine), Green, E.K. (Elaine K), Green, M.J. (Melissa J), Greenwood, T.A. (Tiffany A), Grove, J. (Jakob), Guan, W. (Weihua), Parra, J.G. (José Guzman), Hamshere, M.L. (Marian), Hautzinger, M. (Martin), Heilbronner, U. (Urs), Hipolito, M. (Maria), Holland, D. (Dominic), Huckins, L. (Laura), Jamain, S. (Stéphane), Johnson, J.S. (Jessica S), Juréus, A. (Anders), Kandaswamy, R. (Radhika), Karlsson, R. (Robert), Kennedy, J.L. (James L), Kittel-Schneider, S. (Sarah), Knowles, J.A. (James A), Koller, A.C. (Anna C), Kupka, R.W. (Ralph ), Lavebratt, C. (Catharina), Lawrence, J. (Jacob), Lawson, W.B. (William B), Leber, I. (Isabelle), Lee, P.H. (Phil H), Levy, S.E. (Shawn E), Li, J.Z. (Jun Z), Liu, C. (Chunyu), Lucae, S. (Susanne), Maaser, A. (Anna), Macintyre, D.J. (Donald J), Mahon, P.B. (Pamela B), Maier, W. (Wolfgang), Martinsson, L. (Lina), McCarroll, S.A. (Steve), McGuffin, P. (Peter), Mcinnis, M.G. (Melvin G), McKay, J.D. (James D), Medeiros, H. (Helena), Medland, S.E. (Sarah E), Meng, F. (Fan), Milani, L. (Lili), Montgomery, G.W. (Grant W), Morris, D.W. (Derek W), Mühleisen, T.W. (Thomas W), Mullins, N. (Niamh), Nguyen, H. (Hoang), Nievergelt, C.M. (Caroline M), Adolfsson, A.N. (Annelie Nordin), Nwulia, E.A. (Evaristus A), O’Donovan, C. (Claire), Loohuis, L.M.O. (Loes M Olde), Ori, A.P.S. (Anil P S), Oruc, L. (Lilijana), Ösby, U. (Urban), Perlis, R.H. (Roy H), Perry, A. (Amy), Pfennig, A. (Andrea), Potash, J.B. (James B), Purcell, S.M. (Shaun M), Regeer, E.J. (Eline Janet), Reif, A. (Andreas), Reinbold, C.S. (Céline S), Rice, J.P. (John), Richards, A. (Alex), Rivas, F. (Fabio), Rivera, M. (Margarita), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Ryu, J. (Julie), Sánchez-Mora, C. (Cristina), Schatzberg, A.F. (Alan F), Scheftner, W.A. (William A), Schork, N.J. (Nicholas), Weickert, C.S. (Cynthia Shannon), Shehktman, T. (Tatyana), Shilling, P.D. (Paul D), Sigurdsson, E. (Engilbert), Slaney, C. (Claire), Smeland, O.B. (Olav B), Sobell, J.L. (Janet L), Hansen, C.S. (Christine Søholm), Spijker, A.T. (Anne T), Clair, D.S., Steffens, M. (Michael), Strauss, J.S. (John S), Szelinger, S. (Szabolcs), Thompson, R.C. (Robert C), EThorgeirsson, T. (Thorgeir), Vedde, H. (Helmut), Wang, W. (Weiqing), Watson, S.J. (Stanley J), Weickert, T.W. (Thomas W), Xi, S. (Simon), Xu, W. (Wei), Young, A.H. (Allan H), Zandi, P.P. (Peter P), Zhang, P. (Ping), Zöllner, S. (Sebastian), Adolfsson, R., Agartz, I. (Ingrid), Alda, M. (Martin), Backlund, L. (Lena), Baune, B.T. (Bernhard T), Bellivier, F. (Frank), Berrettini, W. (Wade), Biernacka, J.M. (Joanna M), Blackwood, D.H.R. (Douglas), Boehnke, M. (Michael), Børglum, A.D. (Anders D), Corvin, A. (Aiden), Craddock, N. (Nicholas), Daly, M.J. (Mark), Dannlowski, U. (Udo), Esko, T. (Tõnu), Etain, B. (Bruno), Frye, M.A. (Mark A), Fullerton, J.M. (Janice M), Gershon, E.S. (Elliot S), Gill, M. (Michael), Goes, F. (Fernando), Grigoroiu-Serbanescu, M. (Maria), Hauser, J. (J.), Hougaard, D.M. (David M), Hultman, C.M. (Christina), Jones, I. (Ian), Jones, L.A. (Lisa A), Kahn, R. (René), Kirov, G. (George), Landén, M. (Mikael), Leboyer, M. (Marion), Lewis, C.M. (Cathryn), Li, Q.S. (Qingqin S), Lissowska, J. (Jolanta), Martin, N.G. (Nicholas), Mayoral, F. (Fermin), McElroy, S.L. (Susan L), McIntosh, A.M. (Andrew), Mcmahon, F.J. (Francis J), Melle, I. (Ingrid), Metspalu, A. (Andres), Mitchell, P.B. (Philip B), Morken, G. (Gunnar), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (Bertram), Myers, R.H. (Richard), Neale, B.M. (Benjamin), Nimgaonkar, V. (Vishwajit), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C), Oedegaard, K.J. (Ketil J), Owen, M.J. (Michael J), Paciga, S.A. (Sara A), Pato, C. (Carlos), Posthuma, D. (Danielle), Ramos-Quiroga, J.A. (Josep Antoni), Ribasés, M. (Marta), Rietschel, M. (Marcella), Rouleau, G.A. (Guy A), Schalling, M. (Martin), Schofield, P.R. (Peter R), Schulze, T.G. (Thomas G), Serretti, A. (Alessandro), Smoller, J.W., Stefansson, H. (Hreinn), Zwart, J-A. (John-Anker), Stordal, E. (Eystein), Sullivan, P.F. (Patrick F), Turecki, G. (Gustavo), Vaaler, A.E. (Arne E), Vieta, E. (Eduard), Vincent, J.B. (John B), Werge, T.M. (Thomas), Nurnberger, J.I. (John I), Wray, N.R. (Naomi), Florio, A.D. (Arianna Di), Edenberg, H.J. (Howard), Ophoff, R.A. (Roel), Scott, L.J. (Laura J), Andreassen, O.A. (Ole), Kelsoe, J.R. (John), Sklar, P. (Pamela), Wray, N.R. (Naomi R), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J), Air, T.M. (Tracy M), Bacanu, S.A. (Silviu), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B), Binder, E.B. (Elisabeth), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E), Davies, G. (Gail), Deary, I.J. (Ian J), Degenhardt, F., Derks, E.M. (Eske M), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K), Foo, J.C. (Jerome C), Goes, F.S. (Fernando S), Gordon, S.D. (Scott D.), Hall, L.S. (Lynsey S), Hansen, T.F. (Thomas F), Hickie, I.B. (Ian), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M), Ising, M. (Marcus), Jansen, R. (Rick), Jones, I., Jones, L. (Louisa), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), MacIntyre, D.J. (Donald J), MacKinnon, D.F. (Dean F), Maier, R.M. (Robert M), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Mcguffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel M), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Mondimore, F.M. (Francis M), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (Carsten Bøcker), Peterson, R.E. (Roseann E), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Quiroz, J.A. (Jorge A), Qvist, P. (Per), Rice, J.P. (John P), Riley, B.P. (Brien P.), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C), Shen, L. (Li), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sinnamon, G.C.B. (Grant C B), Smith, A.V. (Davey), Smith, D.J. (Daniel J), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A), Thorgeirsson, T.E. (Thorgeir E), Traylor, M. (Matthew), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M), Viktorin, A. (Alexander), Visscher, P.M. (Peter M), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Wu, Y. (Yang), Xi, H.S. (Hualin S), Yang, J. (Joanna), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Domenici, E. (Enrico), Domschke, K. (Katharina), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas G), McIntosh, A.M. (Andrew M), Mors, O., Müller-Myhsok, B. (B.), Nöthen, M.M. (Markus M), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Porteous, D.J. (David J.), Preisig, M. (Martin), Schaefer, C. (Catherine), Smoller, J.W. (Jordan W), Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn M), Levinson, D.F. (Douglas F.), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick), Mayoral, F. (Fermín), Muller-Myhsok, B. (B.), Forstner, A.J. (Andreas J.), and Nöthen, M.M. (Markus M.)
Abstract: Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
Published: 2019
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10. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author: Glanville, K.P. (Kylie P.), Coleman, J.R.I. (Jonathan R.I.), Hanscombe, K.B. (Ken B.), Euesden, J. (Jack), Choi, S.W. (Shing Wan), Purves, K.L. (Kirstin L.), Breen, G. (Gerome), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F.M.), Baune, B.T., Binder, E.B. (Elisabeth), Blackwood, D.H.R. (Douglas), Boomsma, D.I. (Dorret), Buttenschøn, H.N. (Henriette N.), Colodro-Conde, L. (Lucía), Dannlowski, U. (Udo), Direk, N. (Nese), Dunn, E.C. (Erin C.), Forstner, A.J. (Andreas J.), Geus, E.J.C. (Eco) de, Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Jones, I., Jones, L. (Louisa), Knowles, J.A. (James A), Kutalik, Z. (Zoltán), Levinson, D.F. (Douglas F.), Lewis, G., Lind, P.A. (Penelope), Lucae, S. (Susanne), Magnusson, P.K. (Patrik), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), Milaneschi, Y. (Yuri), Mors, O., Mostafavi, S. (Sara), Müller-Myhsok, B. (B.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Potash, J.B. (James B), Preisig, M. (Martin), Ripke, S. (Stephan), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Smoller, J.W., Streit, F. (Fabian), Sullivan, P.F. (Patrick), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Van der Auwera, S. (Sandra), Weissman, M.M., Wray, N.R. (Naomi), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Bryois, J. (Julien), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian J.), Degenhardt, F., Derks, E.M. (Eske), Dolan, C.V. (Conor), Eley, T.C. (T.), Escott-Price, V. (Valentina), Hassan Kiadeh, F.F. (Farnush Farhadi), Finucane, H.K. (Hilary K.), Foo, J.C. (Jerome C.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Li, Y. (Yihan), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O'Reilly, P.F. (Paul), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Li), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C.B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (Andrés G.), Umbricht, D. (Daniel), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Berger, K. (Klaus), Cichon, S. (Sven), de Geus, E.J.C. (E. J.C.), DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Li, Q.S. (Qingqin S.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Mortensen, P.B. (Preben Bo), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O'donovan, M.C. (Michael), Paciga, S.A. (Sara A.), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Zwart, J-A. (John-Anker), Völzke, H. (Henry), Werge, T.M. (Thomas), Lewis, C.M. (Cathryn), Borglum, A.D. (Anders), Glanville, K.P. (Kylie P.), Coleman, J.R.I. (Jonathan R.I.), Hanscombe, K.B. (Ken B.), Euesden, J. (Jack), Choi, S.W. (Shing Wan), Purves, K.L. (Kirstin L.), Breen, G. (Gerome), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F.M.), Baune, B.T., Binder, E.B. (Elisabeth), Blackwood, D.H.R. (Douglas), Boomsma, D.I. (Dorret), Buttenschøn, H.N. (Henriette N.), Colodro-Conde, L. (Lucía), Dannlowski, U. (Udo), Direk, N. (Nese), Dunn, E.C. (Erin C.), Forstner, A.J. (Andreas J.), Geus, E.J.C. (Eco) de, Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Jones, I., Jones, L. (Louisa), Knowles, J.A. (James A), Kutalik, Z. (Zoltán), Levinson, D.F. (Douglas F.), Lewis, G., Lind, P.A. (Penelope), Lucae, S. (Susanne), Magnusson, P.K. (Patrik), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), Milaneschi, Y. (Yuri), Mors, O., Mostafavi, S. (Sara), Müller-Myhsok, B. (B.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Potash, J.B. (James B), Preisig, M. (Martin), Ripke, S. (Stephan), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Smoller, J.W., Streit, F. (Fabian), Sullivan, P.F. (Patrick), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Van der Auwera, S. (Sandra), Weissman, M.M., Wray, N.R. (Naomi), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Bryois, J. (Julien), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian J.), Degenhardt, F., Derks, E.M. (Eske), Dolan, C.V. (Conor), Eley, T.C. (T.), Escott-Price, V. (Valentina), Hassan Kiadeh, F.F. (Farnush Farhadi), Finucane, H.K. (Hilary K.), Foo, J.C. (Jerome C.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David), Howard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Kohane, I.S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Li, Y. (Yihan), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O'Reilly, P.F. (Paul), Oskarsson, H. (Hogni), Owen, M.J. (Michael), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Li), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C.B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (Andrés G.), Umbricht, D. (Daniel), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Berger, K. (Klaus), Cichon, S. (Sven), de Geus, E.J.C. (E. J.C.), DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Li, Q.S. (Qingqin S.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Mortensen, P.B. (Preben Bo), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O'donovan, M.C. (Michael), Paciga, S.A. (Sara A.), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Zwart, J-A. (John-Anker), Völzke, H. (Henry), Werge, T.M. (Thomas), Lewis, C.M. (Cathryn), and Borglum, A.D. (Anders)
Abstract: Background: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. Methods: We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4). Results: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99). Conclusions: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.
Published: 2019
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11. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author: Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J.A. (James A), Kohane, I.S., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Smoller, J.W., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), Binder, E.B. (Elisabeth), Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J.A. (James A), Kohane, I.S., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Smoller, J.W., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), and Binder, E.B. (Elisabeth)
Abstract: Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
Published: 2019
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12. Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls-CORRIGENDUM

Author: Pettersson, E., Lichtenstein, P., Larsson, H., Song, J., Agrawal, A., Borglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardinãs, A. F., Stahl, E., Walters, J. T.R., Walters, R., Sullivan, P. F., Posthuma, D., Polderman, T. J.C., Pettersson, E., Lichtenstein, P., Larsson, H., Song, J., Agrawal, A., Borglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardinãs, A. F., Stahl, E., Walters, J. T.R., Walters, R., Sullivan, P. F., Posthuma, D., and Polderman, T. J.C.
Published: 2019
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13. Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Author: Foo, JC, Streit, F, Frank, J, Witt, SH, Treutlein, J, Baune, BT, Moebus, S, Joeckel, K-H, Forstner, AJ, Noethen, MM, Rietschel, M, Sartorius, A, Kranaster, L, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, Sullivan, PF, Foo, JC, Streit, F, Frank, J, Witt, SH, Treutlein, J, Baune, BT, Moebus, S, Joeckel, K-H, Forstner, AJ, Noethen, MM, Rietschel, M, Sartorius, A, Kranaster, L, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, and Sullivan, PF
Abstract: Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings.
Published: 2019

14. Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

Author: Arnau-Soler, A, Macdonald-Dunlop, E, Adams, MJ, Clarke, T-K, MacIntyre, DJ, Milburn, K, Navrady, L, Hayward, C, McIntosh, AM, Thomson, PA, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenscon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Rawford, GEC, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, Macintyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, ASD, Sullivan, PF, Arnau-Soler, A, Macdonald-Dunlop, E, Adams, MJ, Clarke, T-K, MacIntyre, DJ, Milburn, K, Navrady, L, Hayward, C, McIntosh, AM, Thomson, PA, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenscon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Rawford, GEC, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Foo, JC, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, Macintyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, ASD, and Sullivan, PF
Abstract: Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10-6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10-9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10-8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10-8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10-6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10-3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
Published: 2019

15. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author: Czamara, D, Eraslan, G, Page, CM, Lahti, J, Lahti-Pulkkinen, M, Hamalainen, E, Kajantie, E, Laivuori, H, Villa, PM, Reynolds, RM, Nystad, W, Haberg, SE, London, SJ, O'Donnell, KJ, Garg, E, Meaney, MJ, Entringer, S, Wadhwa, PD, Buss, C, Jones, MJ, Lin, DTS, MacIsaac, JL, Kobor, MS, Koen, N, Zar, HJ, Koenen, KC, Dalvie, S, Stein, DJ, Kondofersky, I, Mueller, NS, Theis, FJ, Raikkonen, K, Binder, EB, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, Sullivan, PF, Czamara, D, Eraslan, G, Page, CM, Lahti, J, Lahti-Pulkkinen, M, Hamalainen, E, Kajantie, E, Laivuori, H, Villa, PM, Reynolds, RM, Nystad, W, Haberg, SE, London, SJ, O'Donnell, KJ, Garg, E, Meaney, MJ, Entringer, S, Wadhwa, PD, Buss, C, Jones, MJ, Lin, DTS, MacIsaac, JL, Kobor, MS, Koen, N, Zar, HJ, Koenen, KC, Dalvie, S, Stein, DJ, Kondofersky, I, Mueller, NS, Theis, FJ, Raikkonen, K, Binder, EB, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O'Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Borglum, AD, and Sullivan, PF
Abstract: Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
Published: 2019

16. Genetic and environmental contribution to the overlap between ADHD and ASD trait dimensions in young adults: a twin study.

Author: Ghirardi, L., Pettersson, E., Taylor, M.J., Freitag, C.M., Franke, B., Asherson, P., Larsson, H., Kuja-Halkola, R., Ghirardi, L., Pettersson, E., Taylor, M.J., Freitag, C.M., Franke, B., Asherson, P., Larsson, H., and Kuja-Halkola, R.
Abstract: 01 juli 2019, Contains fulltext : 207153.pdf (publisher's version ) (Open Access), BACKGROUND: Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults. METHODS: We studied 6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components. RESULTS: At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31-0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI 0.21-0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23-0.43). CONCLUSIONS: We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.
Published: 2019

17. Genetic and environmental contribution to the overlap between ADHD and ASD trait dimensions in young adults: a twin study.

Author: Ghirardi, L., Pettersson, E., Taylor, M.J., Freitag, C.M., Franke, B., Asherson, P., Larsson, H., Kuja-Halkola, R., Ghirardi, L., Pettersson, E., Taylor, M.J., Freitag, C.M., Franke, B., Asherson, P., Larsson, H., and Kuja-Halkola, R.
Abstract: 01 juli 2019, Contains fulltext : 207153.pdf (publisher's version ) (Open Access), BACKGROUND: Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults. METHODS: We studied 6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components. RESULTS: At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31-0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI 0.21-0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23-0.43). CONCLUSIONS: We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.
Published: 2019

18. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author: Czamara, D. (Darina), Eraslan, G. (Goekcen), Page, C. M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hamalainen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Reynolds, R. M. (Rebecca M.), Nystad, W. (Wenche), Haberg, S. E. (Siri E.), London, S. J. (Stephanie J.), O'Donnell, K. J. (Kieran J.), Garg, E. (Elika), Meaney, M. J. (Michael J.), Entringer, S. (Sonja), Wadhwa, P. D. (Pathik D.), Buss, C. (Claudia), Jones, M. J. (Meaghan J.), Lin, D. T. (David T. S.), MacIsaac, J. L. (Julie L.), Kobor, M. S. (Michael S.), Koen, N. (Nastassja), Zar, H. J. (Heather J.), Koenen, K. C. (Karestan C.), Dalvie, S. (Shareefa), Stein, D. J. (Dan J.), Kondofersky, I. (Ivan), Mueller, N. S. (Nikola S.), Theis, F. J. (Fabian J.), Raikkonen, K. (Katri), Binder, E. B. (Elisabeth B.), Wray, N. R. (Naomi R.), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E. M. (Enda M.), Abdellaoui, A. (Abdel), Adams, M. J. (Mark J.), Agerbo, E. (Esben), Air, T. M. (Tracy M.), Andlauer, T. F. (Till F. M.), Bacanu, S.-A. (Silviu-Alin), Baekvad-Hansen, M. (Marie), Beekman, A. T. (Aartjan T. F.), Bigdeli, T. B. (Tim B.), Blackwood, D. H. (Douglas H. R.), Bryois, J. (Julien), Buttenschon, H. N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J. H. (Jane Hvarregaard), Clarke, T.-K. (Toni-Kim), Coleman, J. R. (Jonathan R., I), Colodro-Conde, L. (Lucia), Couvy-Duchesne, B. (Baptiste), Craddock, N. (Nick), Crawford, G. E. (Gregory E.), Davies, G. (Gail), Deary, I. J. (Ian J.), Degenhardt, F. (Franziska), Derks, E. M. (Eske M.), Direk, N. (Nese), Dolan, C. V. (Conor, V), Dunn, E. C. (Erin C.), Eley, T. C. (Thalia C.), Escott-Price, V. (Valentina), Kiadeh, F. F. (Farnush Farhadi Hassan), Finucane, H. K. (Hilary K.), Forstner, A. J. (Andreas J.), Frank, J. (Josef), Gaspar, H. A. (Helena A.), Gill, M. (Michael), Goes, F. S. (Fernando S.), Gordon, S. D. (Scott D.), Grove, J. (Jakob), Hall, L. S. (Lynsey S.), Hansen, C. S. (Christine Soholm), Hansen, T. F. (Thomas F.), Herms, S. (Stefan), Hickie, I. B. (Ian B.), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.-J. (Jouke-Jan), Hougaard, D. M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J. A. (James A.), Kohane, I. S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W. W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltan), Li, Y. (Yihan), Lind, P. A. (Penelope A.), MacIntyre, D. J. (Donald J.), MacKinnon, D. F. (Dean F.), Maier, R. M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H. (Hamdi), McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S. E. (Sarah E.), Mehta, D. (Divya), Middeldorp, C. M. (Christel M.), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F. M. (Francis M.), Montgomery, G. W. (Grant W.), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. G. (Michel G.), Nyholt, D. R. (Dale R.), O'Reilly, P. F. (Paul F.), Oskarsson, H. (Hogni), Owen, M. J. (Michael J.), Painter, J. N. (Jodie N.), Pedersen, C. B. (Carsten Bocker), Pedersen, M. G. (Marianne Girtz), Peterson, R. E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W. J. (Wouter J.), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J. A. (Jorge A.), Qvist, P. (Per), Rice, J. P. (John P.), Riley, B. P. (Brien P.), Rivera, M. (Margarita), Mirza, S. S. (Saira Saeed), Schoevers, R. (Robert), Schulte, E. C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S. I. (Stanley, I), Sigurdsson, E. (Engilbert), Sinnamon, G. C. (Grant C. B.), Smit, J. H. (Johannes H.), Smith, D. J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K. E. (Katherine E.), Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W. (Wesley), Thomson, P. A. (Pippa A.), Thorgeirsson, T. E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A. G. (Andre G.), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A. M. (Albert M.), Viktorin, A. (Alexander), Visscher, P. M. (Peter M.), Wang, Y. (Yunpeng), Webb, B. T. (Bradley T.), Weinsheimer, S. M. (Shantel Marie), Wellmann, J. (Juergen), Willemsen, G. (Gonneke), Witt, S. H. (Stephanie H.), Wu, Y. (Yang), Xi, H. S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B. T. (Bernhard T.), Berger, K. (Klaus), Boomsma, D. I. (Dorret, I), Cichon, S. (Sven), Dannlowski, U. (Udo), de Geus, E. J. (E. J. C.), DePaulo, J. R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tonu), Grabe, H. J. (Hans J.), Hamilton, S. P. (Steven P.), Hayward, C. (Caroline), Heath, A. C. (Andrew C.), Kendler, K. S. (Kenneth S.), Kloiber, S. (Stefan), Lewis, G. (Glyn), Li, Q. S. (Qingqin S.), Lucae, S. (Susanne), Madden, P. A. (Pamela A. F.), Magnusson, P. K. (Patrik K.), Martin, N. G. (Nicholas G.), McIntosh, A. M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P. B. (Preben Bo), Mueller-Myhsok, B. (Bertram), Nordentoft, M. (Merete), Noethen, M. M. (Markus M.), O'Donovan, M. C. (Michael C.), Paciga, S. A. (Sara A.), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W. J. H.), Perlis, R. H. (Roy H.), Porteous, D. J. (David J.), Potash, J. B. (James B.), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T. G. (Thomas G.), Smoller, J. W. (Jordan W.), Stefansson, K. (Kari), Tiemeier, H. (Henning), Uher, R. (Rudolf), Voelzke, H. (Henry), Weissman, M. M. (Myrna M.), Werge, T. (Thomas), Lewis, C. M. (Cathryn M.), Levinson, D. F. (Douglas F.), Breen, G. (Gerome), Borglum, A. D. (Anders D.), Sullivan, P. F. (Patrick F.), Czamara, D. (Darina), Eraslan, G. (Goekcen), Page, C. M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hamalainen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Reynolds, R. M. (Rebecca M.), Nystad, W. (Wenche), Haberg, S. E. (Siri E.), London, S. J. (Stephanie J.), O'Donnell, K. J. (Kieran J.), Garg, E. (Elika), Meaney, M. J. (Michael J.), Entringer, S. (Sonja), Wadhwa, P. D. (Pathik D.), Buss, C. (Claudia), Jones, M. J. (Meaghan J.), Lin, D. T. (David T. S.), MacIsaac, J. L. (Julie L.), Kobor, M. S. (Michael S.), Koen, N. (Nastassja), Zar, H. J. (Heather J.), Koenen, K. C. (Karestan C.), Dalvie, S. (Shareefa), Stein, D. J. (Dan J.), Kondofersky, I. (Ivan), Mueller, N. S. (Nikola S.), Theis, F. J. (Fabian J.), Raikkonen, K. (Katri), Binder, E. B. (Elisabeth B.), Wray, N. R. (Naomi R.), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E. M. (Enda M.), Abdellaoui, A. (Abdel), Adams, M. J. (Mark J.), Agerbo, E. (Esben), Air, T. M. (Tracy M.), Andlauer, T. F. (Till F. M.), Bacanu, S.-A. (Silviu-Alin), Baekvad-Hansen, M. (Marie), Beekman, A. T. (Aartjan T. F.), Bigdeli, T. B. (Tim B.), Blackwood, D. H. (Douglas H. R.), Bryois, J. (Julien), Buttenschon, H. N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J. H. (Jane Hvarregaard), Clarke, T.-K. (Toni-Kim), Coleman, J. R. (Jonathan R., I), Colodro-Conde, L. (Lucia), Couvy-Duchesne, B. (Baptiste), Craddock, N. (Nick), Crawford, G. E. (Gregory E.), Davies, G. (Gail), Deary, I. J. (Ian J.), Degenhardt, F. (Franziska), Derks, E. M. (Eske M.), Direk, N. (Nese), Dolan, C. V. (Conor, V), Dunn, E. C. (Erin C.), Eley, T. C. (Thalia C.), Escott-Price, V. (Valentina), Kiadeh, F. F. (Farnush Farhadi Hassan), Finucane, H. K. (Hilary K.), Forstner, A. J. (Andreas J.), Frank, J. (Josef), Gaspar, H. A. (Helena A.), Gill, M. (Michael), Goes, F. S. (Fernando S.), Gordon, S. D. (Scott D.), Grove, J. (Jakob), Hall, L. S. (Lynsey S.), Hansen, C. S. (Christine Soholm), Hansen, T. F. (Thomas F.), Herms, S. (Stefan), Hickie, I. B. (Ian B.), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.-J. (Jouke-Jan), Hougaard, D. M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J. A. (James A.), Kohane, I. S. (Isaac S.), Kraft, J. (Julia), Kretzschmar, W. W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltan), Li, Y. (Yihan), Lind, P. A. (Penelope A.), MacIntyre, D. J. (Donald J.), MacKinnon, D. F. (Dean F.), Maier, R. M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H. (Hamdi), McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S. E. (Sarah E.), Mehta, D. (Divya), Middeldorp, C. M. (Christel M.), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F. M. (Francis M.), Montgomery, G. W. (Grant W.), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. G. (Michel G.), Nyholt, D. R. (Dale R.), O'Reilly, P. F. (Paul F.), Oskarsson, H. (Hogni), Owen, M. J. (Michael J.), Painter, J. N. (Jodie N.), Pedersen, C. B. (Carsten Bocker), Pedersen, M. G. (Marianne Girtz), Peterson, R. E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W. J. (Wouter J.), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J. A. (Jorge A.), Qvist, P. (Per), Rice, J. P. (John P.), Riley, B. P. (Brien P.), Rivera, M. (Margarita), Mirza, S. S. (Saira Saeed), Schoevers, R. (Robert), Schulte, E. C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S. I. (Stanley, I), Sigurdsson, E. (Engilbert), Sinnamon, G. C. (Grant C. B.), Smit, J. H. (Johannes H.), Smith, D. J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K. E. (Katherine E.), Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W. (Wesley), Thomson, P. A. (Pippa A.), Thorgeirsson, T. E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A. G. (Andre G.), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A. M. (Albert M.), Viktorin, A. (Alexander), Visscher, P. M. (Peter M.), Wang, Y. (Yunpeng), Webb, B. T. (Bradley T.), Weinsheimer, S. M. (Shantel Marie), Wellmann, J. (Juergen), Willemsen, G. (Gonneke), Witt, S. H. (Stephanie H.), Wu, Y. (Yang), Xi, H. S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B. T. (Bernhard T.), Berger, K. (Klaus), Boomsma, D. I. (Dorret, I), Cichon, S. (Sven), Dannlowski, U. (Udo), de Geus, E. J. (E. J. C.), DePaulo, J. R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tonu), Grabe, H. J. (Hans J.), Hamilton, S. P. (Steven P.), Hayward, C. (Caroline), Heath, A. C. (Andrew C.), Kendler, K. S. (Kenneth S.), Kloiber, S. (Stefan), Lewis, G. (Glyn), Li, Q. S. (Qingqin S.), Lucae, S. (Susanne), Madden, P. A. (Pamela A. F.), Magnusson, P. K. (Patrik K.), Martin, N. G. (Nicholas G.), McIntosh, A. M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P. B. (Preben Bo), Mueller-Myhsok, B. (Bertram), Nordentoft, M. (Merete), Noethen, M. M. (Markus M.), O'Donovan, M. C. (Michael C.), Paciga, S. A. (Sara A.), Pedersen, N. L. (Nancy L.), Penninx, B. W. (Brenda W. J. H.), Perlis, R. H. (Roy H.), Porteous, D. J. (David J.), Potash, J. B. (James B.), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T. G. (Thomas G.), Smoller, J. W. (Jordan W.), Stefansson, K. (Kari), Tiemeier, H. (Henning), Uher, R. (Rudolf), Voelzke, H. (Henry), Weissman, M. M. (Myrna M.), Werge, T. (Thomas), Lewis, C. M. (Cathryn M.), Levinson, D. F. (Douglas F.), Breen, G. (Gerome), Borglum, A. D. (Anders D.), and Sullivan, P. F. (Patrick F.)
Abstract: Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
Published: 2019

19. Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls-CORRIGENDUM

Author: Pettersson, E., Lichtenstein, P., Larsson, H., Song, J., Agrawal, A., Borglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardinãs, A. F., Stahl, E., Walters, J. T.R., Walters, R., Sullivan, P. F., Posthuma, D., Polderman, T. J.C., Pettersson, E., Lichtenstein, P., Larsson, H., Song, J., Agrawal, A., Borglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardinãs, A. F., Stahl, E., Walters, J. T.R., Walters, R., Sullivan, P. F., Posthuma, D., and Polderman, T. J.C.
Published: 2019
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20. Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls

Author: Pettersson, E., Lichtenstein, P., Larsson, Henrik, Song, J., Agrawal, A., Børglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardiñas, A. F., Stahl, E., Walters, J. T. R., Walters, R., Sullivan, P F, Posthuma, D., Polderman, T. J. C., Pettersson, E., Lichtenstein, P., Larsson, Henrik, Song, J., Agrawal, A., Børglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardiñas, A. F., Stahl, E., Walters, J. T. R., Walters, R., Sullivan, P F, Posthuma, D., and Polderman, T. J. C.
Abstract: BACKGROUND: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders. METHODS: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia. RESULTS: Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50. CONCLUSIONS: Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research., Funding Agencies:Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) 340-2013-5867NIMH U01 MH109528 UK Medical Research Council MR/L010305/1 MR/L011794/1 Lundbeck Foundation R102-A9118 R155-2014-1724 Stanley Medical Research Institute European Research Council 294838 Aarhus University Netherlands Organization for Scientific Research NWO VICI 453-14-005 NIMH NIH HHS U01 MH109536 U01 MH109532 U01 MH109528 Medical Research Council MR/L010305/1
Published: 2019
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21. Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls (vol 49, pg 351, 2019)

Author: Pettersson, E., Lichtenstein, P., Larsson, Henrik, Song, J., Agrawal, A., Børglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardinas, A. F., Stahl, E., Walters, J. T. R., Walters, R., Sullivan, P. F., Posthuma, D., Polderman, T. J. C., Pettersson, E., Lichtenstein, P., Larsson, Henrik, Song, J., Agrawal, A., Børglum, A. D., Bulik, C. M., Daly, M. J., Davis, L. K., Demontis, D., Edenberg, H. J., Grove, J., Gelernter, J., Neale, B. M., Pardinas, A. F., Stahl, E., Walters, J. T. R., Walters, R., Sullivan, P. F., Posthuma, D., and Polderman, T. J. C.
Abstract: Funding Agency:NIMH NIH HHS U01 MH109532
Published: 2019
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22. Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Author: Arnau-Soler, A., Adams, M. J., Hayward, C. (Caroline), Thomson, PA, Porteous, D, Campbell, A. (Archie), Smith, B.H. (Blair), Black, C., Padmanabhan, S. (Sandosh), Mcintosh, A.M. (Andrew), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M., Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Agerbo, E, Air, T.M., Andlauer, T.F.M., Bacanu, SA, Bækvad-Hansen, M., Beekman, A.T.F. (Aartjan), Bigdeli, TB, Binder, E.B. (Elisabeth), Blackwood, D.H.R. (Douglas), Bryois, J., Buttenschøn, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E, Christensen, J.H., Clarke, T.-K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N.J. (Nick), Crawford, G.E., Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N., Dolan, C.V. (Conor), Dunn, EC, Eley, T.C. (T.), Escott-Price, V, Kiadeh, F.F.H., Finucane, HK, Forstner, A.J. (Andreas), Frank, J. (Josef), Gaspar, H.A., Gill, M. (Michael), Goes, F.S., Gordon, S.D., Grove, J. (Jakob), Hall, L.S., Hansen, C.S., Hansen, T.F. (Thomas F), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C., Hottenga, JJ, Hougaard, D.M. (David), Ising, M. (Marcus), Jansen, R, Jorgenson, E, Knowles, J.A. (James A), Kohane, IS, Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z. (Zoltán), Li, Y. (Yuwen), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F., Maier, R.M., Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H, McGrath, P., Mcguffin, P. (Peter), Medland, S.E., Mehta, D, Middeldorp, CM, Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M., Montgomery, G.W. (Grant), Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R. (Dale), O'Reilly, P.F. (Paul), Oskarsson, H. (Hogni), Owen, M.J., Painter, JN, Pedersen, CB, Pedersen, M.G., Peterson, R.E., Pettersson, E, Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P. (John), Riley, B.P. (Brien), Rivera, M., Mirza, S.S., Schoevers, R. (Robert), Schulte, E.C., Shen, L. (Li), Shi, J. (Julia), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B., Smit, J.H.M., Smith, D.J. (Derek James), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F., Strohmaier, J., Tansey, KE, Teismann, H., Teumer, A. (Alexander), Thompson, W., Thorgeirsson, T.E. (Thorgeir), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V., Uitterlinden, A.G. (André), Umbricht, D., Van der Auwera, S., van Hemert, A.M., Viktorin, A, Visscher, P.M. (Peter), Wang, Y. (Yijing), Webb, BT, Weinsheimer, S.M., Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y., Xi, HS, Yang, J., Zhang, F. (Feng), Arolt, V, Baune, BT, Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U., de Geus, EJCN, DePaulo, J.R., Domenici, E, Domschke, K., Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Heath, A.C. (Andrew), Kendler, K. (K.), Kloiber, S, Lewis, G, Li, Q.S., Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Mors, O., Mortensen, P.B., Müller-Myhsok, B., Nordentoft, M, Nöthen, M.M. (Markus), O'Donovan, M. (Michael), Paciga, S.A., Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M., Schaefer, C. (Catherine), Schulze, T.G. (Thomas), Smoller, J.W., Zwart, J-A. (John-Anker), Tiemeier, H.W. (Henning), Uher, R, Völzke, H. (Henry), Weissman, M.M. (Myrna M), Werge, T.M. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas), Breen, G. (Gerome), Børglum, A.D., Sullivan, P.F. (Patrick), Arnau-Soler, A., Adams, M. J., Hayward, C. (Caroline), Thomson, PA, Porteous, D, Campbell, A. (Archie), Smith, B.H. (Blair), Black, C., Padmanabhan, S. (Sandosh), Mcintosh, A.M. (Andrew), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M., Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Agerbo, E, Air, T.M., Andlauer, T.F.M., Bacanu, SA, Bækvad-Hansen, M., Beekman, A.T.F. (Aartjan), Bigdeli, TB, Binder, E.B. (Elisabeth), Blackwood, D.H.R. (Douglas), Bryois, J., Buttenschøn, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E, Christensen, J.H., Clarke, T.-K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N.J. (Nick), Crawford, G.E., Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N., Dolan, C.V. (Conor), Dunn, EC, Eley, T.C. (T.), Escott-Price, V, Kiadeh, F.F.H., Finucane, HK, Forstner, A.J. (Andreas), Frank, J. (Josef), Gaspar, H.A., Gill, M. (Michael), Goes, F.S., Gordon, S.D., Grove, J. (Jakob), Hall, L.S., Hansen, C.S., Hansen, T.F. (Thomas F), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C., Hottenga, JJ, Hougaard, D.M. (David), Ising, M. (Marcus), Jansen, R, Jorgenson, E, Knowles, J.A. (James A), Kohane, IS, Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z. (Zoltán), Li, Y. (Yuwen), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F., Maier, R.M., Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H, McGrath, P., Mcguffin, P. (Peter), Medland, S.E., Mehta, D, Middeldorp, CM, Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M., Montgomery, G.W. (Grant), Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R. (Dale), O'Reilly, P.F. (Paul), Oskarsson, H. (Hogni), Owen, M.J., Painter, JN, Pedersen, CB, Pedersen, M.G., Peterson, R.E., Pettersson, E, Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P. (John), Riley, B.P. (Brien), Rivera, M., Mirza, S.S., Schoevers, R. (Robert), Schulte, E.C., Shen, L. (Li), Shi, J. (Julia), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B., Smit, J.H.M., Smith, D.J. (Derek James), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F., Strohmaier, J., Tansey, KE, Teismann, H., Teumer, A. (Alexander), Thompson, W., Thorgeirsson, T.E. (Thorgeir), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V., Uitterlinden, A.G. (André), Umbricht, D., Van der Auwera, S., van Hemert, A.M., Viktorin, A, Visscher, P.M. (Peter), Wang, Y. (Yijing), Webb, BT, Weinsheimer, S.M., Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y., Xi, HS, Yang, J., Zhang, F. (Feng), Arolt, V, Baune, BT, Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U., de Geus, EJCN, DePaulo, J.R., Domenici, E, Domschke, K., Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Heath, A.C. (Andrew), Kendler, K. (K.), Kloiber, S, Lewis, G, Li, Q.S., Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Mors, O., Mortensen, P.B., Müller-Myhsok, B., Nordentoft, M, Nöthen, M.M. (Markus), O'Donovan, M. (Michael), Paciga, S.A., Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M., Schaefer, C. (Catherine), Schulze, T.G. (Thomas), Smoller, J.W., Zwart, J-A. (John-Anker), Tiemeier, H.W. (Henning), Uher, R, Völzke, H. (Henry), Weissman, M.M. (Myrna M), Werge, T.M. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas), Breen, G. (Gerome), Børglum, A.D., and Sullivan, P.F. (Patrick)
Abstract: Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of d
Published: 2018
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23. Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Author: de Jong, S, Abdalla Diniz, MJ, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Curtis, C, Newhouse, SJ, Patel, H, Hall, LS, O'Reilly, PF, Belangero, S, Bressan, RA, Breen, G, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, Mcgrath, P, Mcguffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Borglum, AD, Sullivan, PF, Meier, S, Strauss, J, Xu, W, Vincent, JB, Matthews, K, Ferreira, M, O'Dushlaine, C, Purcell, S, Raychaudhuri, S, Ruderfer, DM, Sklar, P, Scott, LJ, Flickinger, M, Burmeister, M, Li, J, Guan, W, Absher, D, Thompson, RC, Meng, FG, Schatzberg, AF, Bunney, WE, Barchas, JD, Watson, SJ, Myers, RM, Akil, H, Boehnke, M, Chambert, K, Moran, J, Scolnick, E, Djurovic, S, Melle, I, Morken, G, Corvin, A, Anjorin, A, Kandaswamy, R, Lawrence, J, McLean, AW, Pickard, BS, Bergen, SE, Nimgaonkar, V, Landen, M, Schalling, M, Osby, U, Backlund, L, Frisen, L, Langstrom, N, Stahl, E, Dobbyn, A, Jamain, S, Etain, B, Bellivier, F, Leber, M, Maaser, A, Fischer, SB, Reinbold, CS, Kittel-Schneider, S, Fullerton, JM, Oruc, L, Para, JG, Mayoral, F, Rivas, F, Czerski, PM, Kammerer-Ciernioch, J, Vedder, H, Borrmann-Hassenbach, M, Pfennig, A, Brennan, P, McKay, JD, Kogevinas, M, Schwarz, M, Schofield, PR, Muehleisen, TW, Schumacher, J, Bauer, M, Wright, A, Mitchell, PB, Hautzinger, M, Kelsoe, JR, Greenwood, TA, Nievergelt, CM, Shilling, PD, Smith, EN, Bloss, CS, Edenberg, HJ, Koller, DL, Gershon, ES, Liu, C, Badner, JA, Scheftner, WA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Rice, J, Byerley, W, McMahon, FJ, Lohoff, FW, Zandi, PP, Mahon, PB, McInnis, MG, Zollner, S, Zhang, P, Szelinger, S, St Clair, D, Caesar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Kirov, G, Nikolov, I, Collier, DA, Elkin, A, Williamson, R, Young, AH, Ferrier, IN, Milanova, V, Alda, M, Cervantes, P, Cruceanu, C, Rouleau, GA, Turecki, G, Paciga, S, Winslow, AR, Grigoroiu-Serbanescu, M, Ophoff, R, Adolfsson, R, Adolfsson, AN, Del-Favero, J, Pato, C, Biernacka, JM, Frye, MA, Morris, D, Schork, NJ, Reif, A, Lissowska, J, Hauser, J, Szeszenia-Dabrowska, N, McGhee, K, Quinn, E, Moskvina, V, Holmans, PA, Farmer, A, Kennedy, JL, Andreassen, OA, Mattingsdal, M, Bass, NJ, Gurling, H, McQuillin, A, Breuer, R, Hultman, C, Lichtenstein, P, Huckins, LM, Leboyer, M, Lathrop, M, Nurnberger, J, Steffens, M, Foroud, TM, Berrettini, WH, Craig, DW, Shi, J, de Jong, S, Abdalla Diniz, MJ, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Curtis, C, Newhouse, SJ, Patel, H, Hall, LS, O'Reilly, PF, Belangero, S, Bressan, RA, Breen, G, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Baekvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschon, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JR, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G, Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, C, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jones, I, Jones, LA, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, Mcgrath, P, Mcguffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shyn, S, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, D, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Mueller-Myhsok, B, Nordentoft, M, Noethen, MM, O'Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Voelzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Borglum, AD, Sullivan, PF, Meier, S, Strauss, J, Xu, W, Vincent, JB, Matthews, K, Ferreira, M, O'Dushlaine, C, Purcell, S, Raychaudhuri, S, Ruderfer, DM, Sklar, P, Scott, LJ, Flickinger, M, Burmeister, M, Li, J, Guan, W, Absher, D, Thompson, RC, Meng, FG, Schatzberg, AF, Bunney, WE, Barchas, JD, Watson, SJ, Myers, RM, Akil, H, Boehnke, M, Chambert, K, Moran, J, Scolnick, E, Djurovic, S, Melle, I, Morken, G, Corvin, A, Anjorin, A, Kandaswamy, R, Lawrence, J, McLean, AW, Pickard, BS, Bergen, SE, Nimgaonkar, V, Landen, M, Schalling, M, Osby, U, Backlund, L, Frisen, L, Langstrom, N, Stahl, E, Dobbyn, A, Jamain, S, Etain, B, Bellivier, F, Leber, M, Maaser, A, Fischer, SB, Reinbold, CS, Kittel-Schneider, S, Fullerton, JM, Oruc, L, Para, JG, Mayoral, F, Rivas, F, Czerski, PM, Kammerer-Ciernioch, J, Vedder, H, Borrmann-Hassenbach, M, Pfennig, A, Brennan, P, McKay, JD, Kogevinas, M, Schwarz, M, Schofield, PR, Muehleisen, TW, Schumacher, J, Bauer, M, Wright, A, Mitchell, PB, Hautzinger, M, Kelsoe, JR, Greenwood, TA, Nievergelt, CM, Shilling, PD, Smith, EN, Bloss, CS, Edenberg, HJ, Koller, DL, Gershon, ES, Liu, C, Badner, JA, Scheftner, WA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Rice, J, Byerley, W, McMahon, FJ, Lohoff, FW, Zandi, PP, Mahon, PB, McInnis, MG, Zollner, S, Zhang, P, Szelinger, S, St Clair, D, Caesar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Kirov, G, Nikolov, I, Collier, DA, Elkin, A, Williamson, R, Young, AH, Ferrier, IN, Milanova, V, Alda, M, Cervantes, P, Cruceanu, C, Rouleau, GA, Turecki, G, Paciga, S, Winslow, AR, Grigoroiu-Serbanescu, M, Ophoff, R, Adolfsson, R, Adolfsson, AN, Del-Favero, J, Pato, C, Biernacka, JM, Frye, MA, Morris, D, Schork, NJ, Reif, A, Lissowska, J, Hauser, J, Szeszenia-Dabrowska, N, McGhee, K, Quinn, E, Moskvina, V, Holmans, PA, Farmer, A, Kennedy, JL, Andreassen, OA, Mattingsdal, M, Bass, NJ, Gurling, H, McQuillin, A, Breuer, R, Hultman, C, Lichtenstein, P, Huckins, LM, Leboyer, M, Lathrop, M, Nurnberger, J, Steffens, M, Foroud, TM, Berrettini, WH, Craig, DW, and Shi, J
Abstract: Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
Published: 2018

24. Brief Report: Association Between Autism Spectrum Disorder, Gastrointestinal Problems and Perinatal Risk Factors Within Sibling Pairs

Author: Isaksson, J., Pettersson, E., Kostrzewa, E., Diaz Heijtz, R., Bolte, Sven, Isaksson, J., Pettersson, E., Kostrzewa, E., Diaz Heijtz, R., and Bolte, Sven
Abstract: Â© 2017, Springer Science+Business Media New York. Autism spectrum disorder (ASD) has been associated with gastrointestinal (GI) problems, but the nature of this association is unclear. Parents to siblings, concordant or discordant for ASD (N = 217), participated in a web survey covering motherâ€™s weight gain during pregnancy, maternal viral/bacterial infection and use of antibiotics, duration of breastfeeding, mode of delivery, birth weight and child GI problems. ASD was associated with GI problems and perinatal environmental risk, based on a summation of maternal infection and antibiotic use during pregnancy and/or the breastfeeding period. The association between GI problems and ASD remained within the sibling pairs (Î² = 1.23; p < .001) in the adjusted model. Our results indicate non-shared environmental effects on the ASD/GI association, but none of the factors examined explained the link.
Published: 2017

25. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., et al., Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., and et al.
Abstract: Contains fulltext : 166013.pdf (publisher's version ) (Open Access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016

26. Meta-analysis of genome-wide association studies for extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. van den, Moor, M.H.M. de, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H.M. de, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156154.pdf (publisher's version ) (Closed access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016

27. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016
Full Text: View/download PDF

28. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., et al., Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., and et al.
Abstract: Contains fulltext : 166013.pdf (publisher's version ) (Open Access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016

29. Meta-analysis of genome-wide association studies for extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. van den, Moor, M.H.M. de, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H.M. de, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156154.pdf (publisher's version ) (Closed access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016

30. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., et al., Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., and et al.
Abstract: Contains fulltext : 166013.pdf (publisher's version ) (Open Access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016

31. Meta-analysis of genome-wide association studies for extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. van den, Moor, M.H.M. de, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H.M. de, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156154.pdf (publisher's version ) (Closed access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016

32. Proximity extension assay immunoassay technology identifies novel serum biomarkers that can diagnose and classify inflammatory bowel diseases : IBD Character Consortium

Author: Kalla, R., Ocklind, A., Petren, C., Nordberg, N., Kennedy, N., Ventham, N., Pettersson, E., Bergemalm, Daniel, Lindstrom, J., Vatn, S., Hjortswang, H., Nimmo, E., Drummond, H., Ricanek, P., Dahl, F., Wilson, D., Jahnsen, J., Gomollon, F., Pierik, M., Soderholm, J., Vatn, M., Halfvarson, Jonas, Satsangi, J., Kalla, R., Ocklind, A., Petren, C., Nordberg, N., Kennedy, N., Ventham, N., Pettersson, E., Bergemalm, Daniel, Lindstrom, J., Vatn, S., Hjortswang, H., Nimmo, E., Drummond, H., Ricanek, P., Dahl, F., Wilson, D., Jahnsen, J., Gomollon, F., Pierik, M., Soderholm, J., Vatn, M., Halfvarson, Jonas, and Satsangi, J.
Published: 2016
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33. Common psychiatric disorders share the same genetic origin : a multivariate sibling study of the Swedish population

Author: Pettersson, E., Larsson, Henrik, Lichtenstein, P., Pettersson, E., Larsson, Henrik, and Lichtenstein, P.
Abstract: Recent studies have shown that different mental-health problems appear to be partly influenced by the same set of genes, which can be summarized by a general genetic factor. To date, such studies have relied on surveys of community-based samples, which could introduce potential biases. The goal of this study was to examine whether a general genetic factor would still emerge when based on a different ascertainment method with different biases from previous studies. We targeted all adults in Sweden (n=3 475 112) using national registers and identified those who had received one or more psychiatric diagnoses after seeking or being forced into mental health care. In order to examine the genetic versus environmental etiology of the general factor, we examined whether participants' full- or half-siblings had also received diagnoses. We focused on eight major psychiatric disorders based on the International Classification of Diseases, including schizophrenia, schizoaffective disorder, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, alcohol use disorder and drug abuse. In addition, we included convictions of violent crimes. Multivariate analyses demonstrated that a general genetic factor influenced all disorders and convictions of violent crimes, accounting for between 10% (attention-deficit/hyperactivity disorder) and 36% (drug abuse) of the variance of the conditions. Thus, a general genetic factor of psychopathology emerges when based on both surveys as well as national registers, indicating that a set of pleiotropic genes influence a variety of psychiatric disorders., Funding Agencies:Swedish Research Council for Health, Working Life, and Welfare
Published: 2016
Full Text: View/download PDF

34. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author: van den Berg, SM, de Moor, MHM, Verweij, KJH, Krueger, RF, Luciano, M, Vasquez, AA, Matteson, LK, Derringer, J, Esko, T, Amin, Najaf, Gordon, SD, Hansell, NK, Hart, AB, Seppala, I, Huffman, JE, Konte, B, Lahti, J, Lee, Max, Miller, M, Nutile, T, Tanaka, T, Teumer, A, Viktorin, A, Wedenoja, J, Abdellaoui, A, Abecasis, GR, Adkins, DE, Agrawal, A, Allik, J, Appel, K, Bigdeli, TB, Busonero, F, Campbell, H, Costa, PT, Smith, GD, Davies, G, de Wit, HJ, Ding, J, Engelhardt, BE, Eriksson, JG, Fedko, IO, Ferrucci, L, Franke, B, Giegling, I, Grucza, R, Hartmann, AM, Heath, AC, Heinonen, K, Henders, AK, Homuth, G, Hottenga, JJ (Jouke Jan), Iacono, WG, Janzing, J, Jokela, M, Karlsson, R, Kemp, JP, Kirkpatrick, MG, Latvala, A, Lehtimaki, T, Liewald, DC, Madden, PAF, Magri, C, Magnusson, PKE, Marten, J, del Maschio, A, Mbarek, H, Medland, SE, Mihailov, E, Milaneschi, Y, Montgomery, GW, Nauck, M, Nivard, MG, Ouwens, KG, Palotie, A, Pettersson, E, Polasek, O, Qian, Y, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Schmidt, CO, Slutske, WS, Sorice, R, Starr, JM, St Pourcain, B, Sutin, AR, Timpson, NJ, Trochet, H, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Wouda, J, Wright, MJ, Zgaga, L, Porteous, D, Minelli, A, Palmer, AA, Rujescu, D, Ciullo, M, Hayward, C, Rudan, I, Metspalu, A, Kaprio, J, Deary, IJ, Raikkonen, K, Wilson, JF, Keltikangas-Jarvinen, L, Bierut, LJ, Hettema, JM, Grabe, HJ, Penninx, BWJH, Duijn, Cornelia, Evans, DM, Schlessinger, D, Pedersen, NL, Terracciano, A, McGue, M, Martin, NG, Boomsma, DI, Generation, Scotland, van den Berg, SM, de Moor, MHM, Verweij, KJH, Krueger, RF, Luciano, M, Vasquez, AA, Matteson, LK, Derringer, J, Esko, T, Amin, Najaf, Gordon, SD, Hansell, NK, Hart, AB, Seppala, I, Huffman, JE, Konte, B, Lahti, J, Lee, Max, Miller, M, Nutile, T, Tanaka, T, Teumer, A, Viktorin, A, Wedenoja, J, Abdellaoui, A, Abecasis, GR, Adkins, DE, Agrawal, A, Allik, J, Appel, K, Bigdeli, TB, Busonero, F, Campbell, H, Costa, PT, Smith, GD, Davies, G, de Wit, HJ, Ding, J, Engelhardt, BE, Eriksson, JG, Fedko, IO, Ferrucci, L, Franke, B, Giegling, I, Grucza, R, Hartmann, AM, Heath, AC, Heinonen, K, Henders, AK, Homuth, G, Hottenga, JJ (Jouke Jan), Iacono, WG, Janzing, J, Jokela, M, Karlsson, R, Kemp, JP, Kirkpatrick, MG, Latvala, A, Lehtimaki, T, Liewald, DC, Madden, PAF, Magri, C, Magnusson, PKE, Marten, J, del Maschio, A, Mbarek, H, Medland, SE, Mihailov, E, Milaneschi, Y, Montgomery, GW, Nauck, M, Nivard, MG, Ouwens, KG, Palotie, A, Pettersson, E, Polasek, O, Qian, Y, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Schmidt, CO, Slutske, WS, Sorice, R, Starr, JM, St Pourcain, B, Sutin, AR, Timpson, NJ, Trochet, H, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Wouda, J, Wright, MJ, Zgaga, L, Porteous, D, Minelli, A, Palmer, AA, Rujescu, D, Ciullo, M, Hayward, C, Rudan, I, Metspalu, A, Kaprio, J, Deary, IJ, Raikkonen, K, Wilson, JF, Keltikangas-Jarvinen, L, Bierut, LJ, Hettema, JM, Grabe, HJ, Penninx, BWJH, Duijn, Cornelia, Evans, DM, Schlessinger, D, Pedersen, NL, Terracciano, A, McGue, M, Martin, NG, Boomsma, DI, and Generation, Scotland
Published: 2016

35. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author: Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., et al., Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., and et al.
Abstract: Contains fulltext : 153372.pdf (publisher's version ) (Closed access), IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.
Published: 2015

36. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

Author: Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15%of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P <.05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identi
Published: 2015
Full Text: View/download PDF

37. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with Major Depressive Disorder

Author: Moor, M.H.M. de, Berg, S.M. van den, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., Boomsma, D.I., Moor, M.H.M. de, Berg, S.M. van den, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156183.pdf (publisher's version ) (Open Access), IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10(-9) in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10(-8)). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10(-12) < P < .05) and MDD (4.02 x 10(-9) < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identifies a novel locus for neuroticism
Published: 2015

38. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author: Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., et al., Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., and et al.
Abstract: Contains fulltext : 153372.pdf (publisher's version ) (Closed access), IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.
Published: 2015

39. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with Major Depressive Disorder

Author: Moor, M.H.M. de, Berg, S.M. van den, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., Boomsma, D.I., Moor, M.H.M. de, Berg, S.M. van den, Verweij, K.J.H., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J.L., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppälä, I., Huffman, J.E., Konte, B., Lahti, J., Lee, M., Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimäki, T., Liewald, D.C., Madden, P.A.F., Magri, C., Magnusson, P.K.E., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., St Pourcain, B., Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D.J., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., Metspalu, A., Kaprio, J., Deary, I.J., Raikkonen, K., Wilson, J.F., Keltikangas-Jarvinen, L., Bierut, L.J., Hettema, J.M., Grabe, H.J., Penninx, B.W.J.H., Duijn, C.M. van, Evans, D.M., Schlessinger, D., Pedersen, N.L., Terracciano, A., McGue, M.K., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156183.pdf (publisher's version ) (Open Access), IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10(-9) in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10(-8)). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10(-12) < P < .05) and MDD (4.02 x 10(-9) < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identifies a novel locus for neuroticism
Published: 2015

40. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author: Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., et al., Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., and et al.
Abstract: Contains fulltext : 153372.pdf (publisher's version ) (Closed access), IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.
Published: 2015

41. Particulate PAH Emissions from Residential Biomass Combustion : Time-Resolved Analysis with Aerosol Mass Spectrometry

Author: Eriksson, A. C., Nordin, E. Z., Nyström, Robin, Pettersson, E., Swietlicki, E., Bergvall, C., Westerholm, R., Boman, Christoffer, Pagels, J. H., Eriksson, A. C., Nordin, E. Z., Nyström, Robin, Pettersson, E., Swietlicki, E., Bergvall, C., Westerholm, R., Boman, Christoffer, and Pagels, J. H.
Abstract: Time-resolved emissions of particulate polycyclic aromatic hydrocarbons (PAHs) and total organic particulate matter (OA) from a wood log stove and an adjusted pellet stove were investigated with high-resolution time-of-flight aerosol mass spectrometry (ANIS). The highest OA emissions were found during the addition of log wood on glowing embers, that is, slow burning pyrolysis conditions. These emissions contained about 1% PAHs (of OA). The highest PAH emissions were found during fast burning under hot air starved combustion conditions, in both stoves. In the latter case, PAHs contributed up to 40% of OA, likely due to thermal degradation of other condensable species. The distribution of PAHs was also shifted toward larger molecules in these emissions. ANIS signals attributed to PAHs were found at molecular weights up to 600 Da. The vacuum aerodynamic size distribution was found to be bimodal with a smaller mode (D-va similar to 200 nm) dominating under hot air starved combustion and a larger sized mode dominating under slow burning pyrolysis (D-va similar to 600 nm). Simultaneous reduction of PAHs, OA and total particulate matter from residential biomass combustion may prove to be a challenge for environmental legislation efforts as these classes of emissions are elevated at different combustion conditions.
Published: 2014
Full Text: View/download PDF

42. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author: Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

43. Particulate PAH Emissions from Residential Biomass Combustion : Time-Resolved Analysis with Aerosol Mass Spectrometry

Author: Eriksson, A. C., Nordin, E. Z., Nyström, R., Pettersson, E., Swietlicki, E., Bergvall, Christoffer, Westerholm, Roger, Boman, C., Pagels, J. H., Eriksson, A. C., Nordin, E. Z., Nyström, R., Pettersson, E., Swietlicki, E., Bergvall, Christoffer, Westerholm, Roger, Boman, C., and Pagels, J. H.
Abstract: Time-resolved emissions of particulate polycyclic aromatic hydrocarbons (PAHs) and total organic particulate matter (OA) from a wood log stove and an adjusted pellet stove were investigated with high-resolution time-of-flight aerosol mass spectrometry (AMS). The highest OA emissions were found during the addition of log wood on glowing embers, that is, slow burning pyrolysis conditions. These emissions contained about 1% PAHs (of OA). The highest PAH emissions were found during fast burning under hot air starved combustion conditions, in both stoves. In the latter case, PAHs contributed up to 40% of OA, likely due to thermal degradation of other condensable species. The distribution of PAHs was also shifted toward larger molecules in these emissions. AMS signals attributed to PAHs were found at molecular weights up to 600 Da. The vacuum aerodynamic size distribution was found to be bimodal with a smaller mode (Dva ~ 200 nm) dominating under hot air starved combustion and a larger sized mode dominating under slow burning pyrolysis (Dva ~ 600 nm). Simultaneous reduction of PAHs, OA and total particulate matter from residential biomass combustion may prove to be a challenge for environmental legislation efforts as these classes of emissions are elevated at different combustion conditions.
Published: 2014
Full Text: View/download PDF

44. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author: Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014
Full Text: View/download PDF

45. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author: Berg, S.M. van den, Moor, M.H.M. de, McGue, M.K., Pettersson, E., Terracciano, A., Verweij, K.J.H., Amin, N., Derringer, J.L., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J.E., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J.C. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, L., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H.M. de, McGue, M.K., Pettersson, E., Terracciano, A., Verweij, K.J.H., Amin, N., Derringer, J.L., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J.E., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J.C. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, L., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156156.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in > 160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

46. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author: Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

47. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author: Berg, S.M. van den, Moor, M.H.M. de, McGue, M.K., Pettersson, E., Terracciano, A., Verweij, K.J.H., Amin, N., Derringer, J.L., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J.E., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J.C. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, L.A.L.M., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H.M. de, McGue, M.K., Pettersson, E., Terracciano, A., Verweij, K.J.H., Amin, N., Derringer, J.L., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J.E., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J.C. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, L.A.L.M., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156156.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in > 160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

48. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author: Berg, S.M. van den, Moor, M.H.M. de, McGue, M.K., Pettersson, E., Terracciano, A., Verweij, K.J.H., Amin, N., Derringer, J.L., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J.E., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J.C. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, L.A.L.M., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H.M. de, McGue, M.K., Pettersson, E., Terracciano, A., Verweij, K.J.H., Amin, N., Derringer, J.L., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J.E., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J.C. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, L.A.L.M., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, H.H.M., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 156156.pdf (Publisher’s version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in > 160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

49. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author: Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
Abstract: Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

50. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author: van den Berg, SM, de Moor, MHM, McGue, M, Pettersson, E, Terracciano, A, Verweij, KJH, Amin, Najaf, Derringer, J, Esko, T, Van Grootheest, G, Hansell, NK, Huffman, J, Konte, B, Lahti, J, Luciano, M, Matteson, LK, Viktorin, A, Wouda, J, Agrawal, A, Allik, J, Bierut, L, Broms, U, Campbell, H, Smith, GD, Eriksson, JG, Ferrucci, L, Franke, B, Fox, JP, de Geus, EJC, Giegling, I, Gow, AJ, Grucza, R, Hartmann, AM, Heath, AC, Heikkila, K, Iacono, W, Janzing, J, Jokela, M, Kiemeney, L, Lehtimaki, T, Madden, PAF, Magnusson, PKE, Northstone, K, Nutile, T, Ouwens, KG, Palotie, A, Pattie, A, Pesonen, AK, Polasek, O, Pulkkinen, L, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Seppala, I, Slutske, WS, Smyth, DC, Sorice, R, Starr, JM, Sutin, AR, Tanaka, T, Verhagen, J, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Willemsen, G, Wright, M, Zgaga, L, Rujescu, D, Metspalu, A, Wilson, JF, Ciullo, M, Hayward, C, Rudan, I, Deary, IJ, Raikkonen, K, Vasquez, AA, Costa, PT, Keltikangas-Jarvinen, L, Duijn, Cornelia, Penninx, BWJH, Krueger, RF, Evans, DM, Kaprio, J, Pedersen, NL, Martin, NG, Boomsma, DI, van den Berg, SM, de Moor, MHM, McGue, M, Pettersson, E, Terracciano, A, Verweij, KJH, Amin, Najaf, Derringer, J, Esko, T, Van Grootheest, G, Hansell, NK, Huffman, J, Konte, B, Lahti, J, Luciano, M, Matteson, LK, Viktorin, A, Wouda, J, Agrawal, A, Allik, J, Bierut, L, Broms, U, Campbell, H, Smith, GD, Eriksson, JG, Ferrucci, L, Franke, B, Fox, JP, de Geus, EJC, Giegling, I, Gow, AJ, Grucza, R, Hartmann, AM, Heath, AC, Heikkila, K, Iacono, W, Janzing, J, Jokela, M, Kiemeney, L, Lehtimaki, T, Madden, PAF, Magnusson, PKE, Northstone, K, Nutile, T, Ouwens, KG, Palotie, A, Pattie, A, Pesonen, AK, Polasek, O, Pulkkinen, L, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Seppala, I, Slutske, WS, Smyth, DC, Sorice, R, Starr, JM, Sutin, AR, Tanaka, T, Verhagen, J, Vermeulen, Shanna, Vuoksimaa, E, Widen, E, Willemsen, G, Wright, M, Zgaga, L, Rujescu, D, Metspalu, A, Wilson, JF, Ciullo, M, Hayward, C, Rudan, I, Deary, IJ, Raikkonen, K, Vasquez, AA, Costa, PT, Keltikangas-Jarvinen, L, Duijn, Cornelia, Penninx, BWJH, Krueger, RF, Evans, DM, Kaprio, J, Pedersen, NL, Martin, NG, and Boomsma, DI
Abstract: Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in > 160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014

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