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1. PO-2198 MRI guided nodular salvage Brachytherapy after Prostatectomy and EBRT. 3 years outcome

Author: Willisch Santamaria, P., primary, Andrade Alvarez, B., additional, Cespon Outeda, E., additional, Rojas Bua, L., additional, Vazquez de la Torre Gonzalez, M.L., additional, Lopez Medina, A., additional, Montemuiño Muñiz, S., additional, Martínez Agra, M., additional, Castelao, E., additional, and Muñoz Garzon, V.M., additional
Published: 2023
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2. Inter-informant agreement and prevalence estimates for mood syndromes: Direct interview vs. family history method

Author: Vandeleur, C.L., Rothen, S., Lustenberger, Y., Glaus, J., Castelao, E., and Preisig, M.
Published: 2015
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3. Low emotion-oriented coping and informal help-seeking behaviour as major predictive factors for improvement in major depression at 5-year follow-up in the adult community

Author: Rodgers, S., Vandeleur, C. L., Strippoli, M.-P. F., Castelao, E., Tesic, A., Glaus, J., Lasserre, A. M., Müller, M., Rössler, W., Ajdacic-Gross, V., and Preisig, M.
Published: 2017
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4. Prospective associations of depression subtypes with cardio-metabolic risk factors in the general population

Author: Lasserre, A M, Strippoli, M-P F, Glaus, J, Gholam-Rezaee, M, Vandeleur, C L, Castelao, E, Marques-Vidal, P, Waeber, G, Vollenweider, P, and Preisig, M
Published: 2017
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5. Meta-analysis of genome-wide association studies of anxiety disorders

Author: Otowa, T, Hek, K, Lee, M, Byrne, E M, Mirza, S S, Nivard, M G, Bigdeli, T, Aggen, S H, Adkins, D, Wolen, A, Fanous, A, Keller, M C, Castelao, E, Kutalik, Z, der Auwera, S V, Homuth, G, Nauck, M, Teumer, A, Milaneschi, Y, Hottenga, J-J, Direk, N, Hofman, A, Uitterlinden, A, Mulder, C L, Henders, A K, Medland, S E, Gordon, S, Heath, A C, Madden, P A F, Pergadia, M L, van der Most, P J, Nolte, I M, van Oort, F V A, Hartman, C A, Oldehinkel, A J, Preisig, M, Grabe, H J, Middeldorp, C M, Penninx, B W J H, Boomsma, D, Martin, N G, Montgomery, G, Maher, B S, van den Oord, E J, Wray, N R, Tiemeier, H, and Hettema, J M
Published: 2016
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6. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Mullins, N, Kang, J, Campos, A, Coleman, JR, Edwards, AC, Galfalvy, H, Levey, DF, Lori, A, Shabalin, A, Starnawska, A, Su, M-H, Watson, HJ, Adams, M, Awasthi, S, Ganda, M, Hafferty, JD, Hishimoto, A, Kim, M, Okazaki, S, Otsuka, I, Ripke, S, Ware, EB, Bergen, AW, Berrettini, WH, Bohus, M, Brandt, H, Chang, X, Chen, WJ, Chen, H-C, Crawford, S, Crow, S, DiBlasi, E, Duriez, P, Fernandez-Aranda, F, Fichter, MM, Gallinger, S, Glatt, SJ, Gorwood, P, Guo, Y, Hakonarson, H, Halmi, KA, Hwu, H-G, Jain, S, Jamain, S, Jimenez-Murcia, S, Johnson, C, Kaplan, AS, Kaye, WH, Keel, PK, Kennedy, JL, Klump, KL, Li, D, Liao, S-C, Lieb, K, Lilenfeld, L, Liu, C-M, Magistretti, PJ, Marshall, CR, Mitchell, JE, Monson, ET, Myers, RM, Pinto, D, Powers, A, Ramoz, N, Roepke, S, Rozanov, V, Scherer, SW, Schmahl, C, Sokolowski, M, Strober, M, Thornton, LM, Treasure, J, Tsuang, MT, Witt, SH, Woodside, DB, Yilmaz, Z, Zillich, L, Adolfsson, R, Agartz, I, Air, TM, Alda, M, Alfredsson, L, Andreassen, OA, Anjorin, A, Appadurai, V, Artigas, MS, Van der Auwera, S, Azevedo, MH, Bass, N, Bau, CHD, Baune, BT, Bellivier, F, Berger, K, Biernacka, JM, Bigdeli, TB, Binder, EB, Boehnke, M, Boks, MP, Bosch, R, Braff, DL, Bryant, R, Budde, M, Byrne, EM, Cahn, W, Casas, M, Castelao, E, Cervilla, JA, Chaumette, B, Cichon, S, Corvin, A, Craddock, N, Craig, D, Degenhardt, F, Djurovic, S, Edenberg, HJ, Fanous, AH, Foo, JC, Forstner, AJ, Frye, M, Fullerton, JM, Gatt, JM, Gejman, P, Giegling, I, Grabe, HJ, Green, MJ, Grevet, EH, Grigoroiu-Serbanescu, M, Gutierrez, B, Guzman-Parra, J, Hamilton, SP, Hamshere, ML, Hartmann, A, Hauser, J, Heilmann-Heimbach, S, Hoffmann, P, Ising, M, Jones, I, Jones, LA, Jonsson, L, Kahn, RS, Kelsoe, JR, Kendler, KS, Kloiber, S, Koenen, KC, Kogevinas, M, Konte, B, Krebs, M-O, Lander, M, Lawrence, J, Leboyer, M, Lee, PH, Levinson, DF, Liao, C, Lissowska, J, Lucae, S, Mayoral, F, McElroy, SL, McGrath, P, McGuffin, P, McQuillin, A, Medland, SE, Mehta, D, Melle, I, Milaneschi, Y, Mitchell, PB, Molina, E, Morken, G, Mortensen, PB, Mueller-Myhsok, B, Nievergelt, C, Nimgaonkar, V, Noethen, MM, O'Donovan, MC, Ophoff, RA, Owen, MJ, Pato, C, Pato, MT, Penninx, BWJH, Pimm, J, Pistis, G, Potash, JB, Power, RA, Preisig, M, Quested, D, Ramos-Quiroga, JA, Reif, A, Ribases, M, Richarte, V, Rietschel, M, Rivera, M, Roberts, A, Roberts, G, Rouleau, GA, Rovaris, DL, Rujescu, D, Sanchez-Mora, C, Sanders, AR, Schofield, PR, Schulze, TG, Scott, LJ, Serretti, A, Shi, J, Shyn, S, Sirignano, L, Sklar, P, Smeland, OB, Smoller, JW, Sonuga-Barke, EJS, Spalletta, G, Strauss, JS, Swiatkowska, B, Trzaskowski, M, Turecki, G, Vilar-Ribo, L, Vincent, JB, Voelzke, H, Walters, JTR, Weickert, CS, Weickert, TW, Weissman, MM, Williams, LM, Wray, NR, Zai, CC, Ashley-Koch, AE, Beckham, JC, Hauser, ER, Hauser, MA, Kimbrel, NA, Lindquist, JH, McMahon, B, Oslin, DW, Qin, X, Agerbo, E, Borglum, AD, Breen, G, Erlangsen, A, Esko, T, Gelernter, J, Hougaard, DM, Kessler, RC, Kranzler, HR, Li, QS, Martin, NG, McIntosh, AM, Mors, O, Nordentoft, M, Olsen, CM, Porteous, D, Ursano, RJ, Wasserman, D, Werge, T, Whiteman, DC, Bulik, CM, Coon, H, Demontis, D, Docherty, AR, Kuo, P-H, Lewis, CM, Mann, JJ, Renteria, ME, Smith, DJ, Stahl, EA, Stein, MB, Streit, F, Willour, V, Ruderfer, DM, Mullins, N, Kang, J, Campos, A, Coleman, JR, Edwards, AC, Galfalvy, H, Levey, DF, Lori, A, Shabalin, A, Starnawska, A, Su, M-H, Watson, HJ, Adams, M, Awasthi, S, Ganda, M, Hafferty, JD, Hishimoto, A, Kim, M, Okazaki, S, Otsuka, I, Ripke, S, Ware, EB, Bergen, AW, Berrettini, WH, Bohus, M, Brandt, H, Chang, X, Chen, WJ, Chen, H-C, Crawford, S, Crow, S, DiBlasi, E, Duriez, P, Fernandez-Aranda, F, Fichter, MM, Gallinger, S, Glatt, SJ, Gorwood, P, Guo, Y, Hakonarson, H, Halmi, KA, Hwu, H-G, Jain, S, Jamain, S, Jimenez-Murcia, S, Johnson, C, Kaplan, AS, Kaye, WH, Keel, PK, Kennedy, JL, Klump, KL, Li, D, Liao, S-C, Lieb, K, Lilenfeld, L, Liu, C-M, Magistretti, PJ, Marshall, CR, Mitchell, JE, Monson, ET, Myers, RM, Pinto, D, Powers, A, Ramoz, N, Roepke, S, Rozanov, V, Scherer, SW, Schmahl, C, Sokolowski, M, Strober, M, Thornton, LM, Treasure, J, Tsuang, MT, Witt, SH, Woodside, DB, Yilmaz, Z, Zillich, L, Adolfsson, R, Agartz, I, Air, TM, Alda, M, Alfredsson, L, Andreassen, OA, Anjorin, A, Appadurai, V, Artigas, MS, Van der Auwera, S, Azevedo, MH, Bass, N, Bau, CHD, Baune, BT, Bellivier, F, Berger, K, Biernacka, JM, Bigdeli, TB, Binder, EB, Boehnke, M, Boks, MP, Bosch, R, Braff, DL, Bryant, R, Budde, M, Byrne, EM, Cahn, W, Casas, M, Castelao, E, Cervilla, JA, Chaumette, B, Cichon, S, Corvin, A, Craddock, N, Craig, D, Degenhardt, F, Djurovic, S, Edenberg, HJ, Fanous, AH, Foo, JC, Forstner, AJ, Frye, M, Fullerton, JM, Gatt, JM, Gejman, P, Giegling, I, Grabe, HJ, Green, MJ, Grevet, EH, Grigoroiu-Serbanescu, M, Gutierrez, B, Guzman-Parra, J, Hamilton, SP, Hamshere, ML, Hartmann, A, Hauser, J, Heilmann-Heimbach, S, Hoffmann, P, Ising, M, Jones, I, Jones, LA, Jonsson, L, Kahn, RS, Kelsoe, JR, Kendler, KS, Kloiber, S, Koenen, KC, Kogevinas, M, Konte, B, Krebs, M-O, Lander, M, Lawrence, J, Leboyer, M, Lee, PH, Levinson, DF, Liao, C, Lissowska, J, Lucae, S, Mayoral, F, McElroy, SL, McGrath, P, McGuffin, P, McQuillin, A, Medland, SE, Mehta, D, Melle, I, Milaneschi, Y, Mitchell, PB, Molina, E, Morken, G, Mortensen, PB, Mueller-Myhsok, B, Nievergelt, C, Nimgaonkar, V, Noethen, MM, O'Donovan, MC, Ophoff, RA, Owen, MJ, Pato, C, Pato, MT, Penninx, BWJH, Pimm, J, Pistis, G, Potash, JB, Power, RA, Preisig, M, Quested, D, Ramos-Quiroga, JA, Reif, A, Ribases, M, Richarte, V, Rietschel, M, Rivera, M, Roberts, A, Roberts, G, Rouleau, GA, Rovaris, DL, Rujescu, D, Sanchez-Mora, C, Sanders, AR, Schofield, PR, Schulze, TG, Scott, LJ, Serretti, A, Shi, J, Shyn, S, Sirignano, L, Sklar, P, Smeland, OB, Smoller, JW, Sonuga-Barke, EJS, Spalletta, G, Strauss, JS, Swiatkowska, B, Trzaskowski, M, Turecki, G, Vilar-Ribo, L, Vincent, JB, Voelzke, H, Walters, JTR, Weickert, CS, Weickert, TW, Weissman, MM, Williams, LM, Wray, NR, Zai, CC, Ashley-Koch, AE, Beckham, JC, Hauser, ER, Hauser, MA, Kimbrel, NA, Lindquist, JH, McMahon, B, Oslin, DW, Qin, X, Agerbo, E, Borglum, AD, Breen, G, Erlangsen, A, Esko, T, Gelernter, J, Hougaard, DM, Kessler, RC, Kranzler, HR, Li, QS, Martin, NG, McIntosh, AM, Mors, O, Nordentoft, M, Olsen, CM, Porteous, D, Ursano, RJ, Wasserman, D, Werge, T, Whiteman, DC, Bulik, CM, Coon, H, Demontis, D, Docherty, AR, Kuo, P-H, Lewis, CM, Mann, JJ, Renteria, ME, Smith, DJ, Stahl, EA, Stein, MB, Streit, F, Willour, V, and Ruderfer, DM
Abstract: BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Published: 2022

7. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

Author: Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., Fisher, S.E., Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., and Fisher, S.E.
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Published: 2022

8. National Survey: How Do We Approach the Patient at Risk of Clinical Deterioration outside the ICU in the Spanish Context?

Author: Universitat Rovira i Virgili, Clemente Vivancos Á; León Castelao E; Castellanos Ortega Á; Bodi Saera M; Gordo Vidal F; Martin Delgado MC; Jorge-Soto C; Fernandez Mendez F; Igeño Cano JC; Trenado Alvarez J; Caballero Lopez J; Parraga Ramirez MJ, Universitat Rovira i Virgili, and Clemente Vivancos Á; León Castelao E; Castellanos Ortega Á; Bodi Saera M; Gordo Vidal F; Martin Delgado MC; Jorge-Soto C; Fernandez Mendez F; Igeño Cano JC; Trenado Alvarez J; Caballero Lopez J; Parraga Ramirez MJ
Abstract: Background: Anticipating and avoiding preventable intrahospital cardiac arrest and clinical deterioration are important priorities for international healthcare systems and institutions. One of the internationally followed strategies to improve this matter is the introduction of the Rapid Response Systems (RRS). Although there is vast evidence from the international community, the evidence reported in a Spanish context is scarce. Methods: A nationwide cross-sectional research consisting of a voluntary 31-question online survey was performed. The Spanish Society of Intensive, Critical and Coronary Care Medicine (SEMICYUC) supported the research. Results: We received 62 fully completed surveys distributed within 13 of the 17 regions and two autonomous cities of Spain. Thirty-two of the participants had an established Rapid Response Team (RRT). Common frequency on measuring vital signs was at least once per shift but other frequencies were contemplated (48.4%), usually based on professional criteria (69.4%), as only 12 (19.4%) centers used Early Warning Scores (EWS) or automated alarms on abnormal parameters. In the sample, doctors, nurses (55%), and other healthcare professionals (39%) could activate the RRT via telephone, but only 11.3% of the sample enacted this at early signs of deterioration. The responders on the RRT are the Intensive Care Unit (ICU), doctors, and nurses, who are available 24/7 most of the time. Concerning the education and training of general ward staff and RRT members, this varies from basic to advanced and specific-specialized level, simulating a growing educational methodology among participants. A great number of participants have emergency resuscitation equipment (drugs, airway adjuncts, and defibrillators) in their general wards. In terms of qu
Published: 2022

9. Environmental factors in offspring of parents with mood disorders and their role in parent-child transmission: findings from a 14-year prospective high-risk study

Author: Moulin, F., Gholam, M., Strippoli, M.F., Castelao, E., Merikangas, K.R., Stapp, E.K., Marquet, P., Aubry, J.M., Plessen, K.J., Di Giacomo, F., Glaus, J., Pistis, G., Lavigne, B., Elowe, J., Ranjbar, S., Preisig, M., and Vandeleur, C.L.
Subjects: Biological Psychiatry, Psychiatry and Mental health, Family environment, Offspring of bipolar parents, Offspring of depressed parents, Parental separation, Trauma
Abstract: The factors involved in the transmission of mood disorders are only partially elucidated. Aside from genes, the family environment might play a crucial role in parent-child transmission. Our goals were to (1) assess the associations of parental bipolar disorder (BPD) and Major Depressive Disorder (MDD) with individual or shared family environmental factors, including traumatic events in offspring, parental separation, family cohesion and parental attitudes; and 2) test whether these factors were mediators of the association between exposure to parental mood disorders and the onset of these disorders in offspring. The sample stems from an ongoing family high-risk study of mood disorders conducted in the French-speaking part of Switzerland. Given the strong impact of the age of onset of parental disorders on their transmission to children, parental disorders were dichotomized according to the onset (cut-off 21 years). Probands with early-onset (n = 30) and later-onset BPD (n = 51), early-onset (n = 21) and later-onset MDD (n = 47) and controls (n = 65), along with their spouses (n = 193) and offspring (n = 388; < 18 years on study inclusion), were assessed over a mean follow-up duration of 14 years (s.d: 4.6). The environmental measures were based on reports by offspring collected before the onset of their first mood episode. Offspring of probands with later-onset BPD and offspring of probands with both early-onset and later-onset MDD reported traumatic events more frequently than comparison offspring, whereas exposure to parental separation was more frequent in all groups of high-risk offspring. Moreover, several familial environment scores including parenting attitudes differed between offspring of probands with BPD and comparison offspring. However, none of these factors were mediators of the parent-child transmission of BPD. Among the environmental factors, traumatic events were shown to be modest mediators of the transmission of early-onset MDD. Our data do not support the implication of the assessed environmental factors in the parent-child transmission of BPD. In contrast to BPD, traumatic events partially mediate the parent-child transmission of early-onset MDD, which has important implications for intervention and prevention. Early therapeutic efforts in offspring exposed to these events are likely to reduce their deleterious impact on the risk of subsequent MDD.
Published: 2021

10. Specificity of psychosis, mania and major depression in a contemporary family study

Author: Vandeleur, C L, Merikangas, K R, Strippoli, M-P F, Castelao, E, and Preisig, M
Published: 2014
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11. Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults A 2-Sample Mendelian Randomization Study

Author: Choi, K.W., Chen, C.Y., Stein, M.B., Klimentidis, Y.C., Wang, M.J., Koenen, K.C., Smoller, J.W., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T., Andlauer, T.F.M., Bacanu, S.A., Baekvad-Hansen, M., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenschon, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Hvarregaard, J., Christensen, J.H., Clarke, T.K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Ising, M., Jansen, R., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Marchini, J., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Saeed, S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y.P., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Nordentoft, M., Nothen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.D., Sullivan, P.F., Major Depressive Disorder Working, Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Psychiatry, Biological Psychology, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, and Adult Psychiatry
Subjects: Adult, DISORDER, medicine.medical_specialty, Genome-wide association study, EXERCISE, CAUSALITY, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, PEOPLE, Internal medicine, Accelerometry, Mendelian randomization, SCHIZOPHRENIA, Humans, Medicine, ANXIETY, Exercise, RISK, Depressive Disorder, Major, business.industry, Case-control study, SEDENTARY BEHAVIOR, Mendelian Randomization Analysis, Odds ratio, ASSOCIATION, Protective Factors, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Sample size determination, Case-Control Studies, Meta-analysis, Major depressive disorder, Self Report, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Importance: Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity.Objective: To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference.Design, Setting, and Participants: This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes-self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)-and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in diverse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018.Main Outcomes and Measures: MDD and physical activity.Results: GWAS summary data were available for a combined sample size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in mean acceleration; 95% CI, 0.59-0.92; P = .006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = -0.08 in mean acceleration per MDD vs control status; 95% CI, -0.47 to 0.32; P = .70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity; 95% CI, 0.57-3.37; P = .48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status; 95% CI, -0.008 to 0.05; P = .15).Conclusions and Relevance: Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed-but not self-reported-physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression.
Published: 2019

12. The specificity of mania and early age of onset in high risk youth: a 10 year prospective study

Author: Preisig, M, Vandeleur, C L, Strippoli, M PF, Castelao, E, Gholam-Rezaee, M, Merikangas, K R, Marquet, P, and Aubry, J M
Published: 2015

13. Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk

Author: Miles, AE, Dos Santos, FC, Byrne, EM, Renteria, ME, McIntosh, AM, Adams, MJ, Pistis, G, Castelao, E, Preisig, M, Baune, BT, Schubert, KO, Lewis, CM, Jones, LA, Jones, I, Uher, R, Smoller, JW, Perlis, RH, Levinson, DF, Potash, JB, Weissman, MM, Shi, J, Lewis, G, Penninx, BWJH, Boomsma, D, Hamilton, SP, Sibille, E, Hariri, AR, Nikolova, YS, Miles, AE, Dos Santos, FC, Byrne, EM, Renteria, ME, McIntosh, AM, Adams, MJ, Pistis, G, Castelao, E, Preisig, M, Baune, BT, Schubert, KO, Lewis, CM, Jones, LA, Jones, I, Uher, R, Smoller, JW, Perlis, RH, Levinson, DF, Potash, JB, Weissman, MM, Shi, J, Lewis, G, Penninx, BWJH, Boomsma, D, Hamilton, SP, Sibille, E, Hariri, AR, and Nikolova, YS
Abstract: Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.
Published: 2021

14. Subjective and objective sleep quality in migraine: the Hypnolaus/Psycholaus study: P967

Author: Haba-Rubio, J., Andries, D., Tobback, N., Preisig, M., Castelao, E., Tafti, M., and Heinzer, R.
Published: 2014

15. Sex-related and non-sex-related comorbidity subtypes of tic disorders: a latent class approach

Author: Rodgers, S., Müller, M., Kawohl, W., Knöpfli, D., Rössler, W., Castelao, E., Preisig, M., and Ajdacic-Gross, V.
Published: 2014
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16. 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

17. 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

18. Atypical depression and alcohol misuse are related to the cardiovascular risk in the general population

Author: Glaus, J., Vandeleur, C., Gholam-Rezaee, M., Castelao, E., Perrin, M., Rothen, S., Bovet, P., Marques-Vidal, P., von Känel, R., Merikangas, K., Mooser, V., Waterworth, D. M., Waeber, G., Vollenweider, P., and Preisig, M.
Published: 2013
Full Text: View/download PDF

19. Predictors of mood disorders in the offspring of bipolar probands: RC 1

Author: Preisig, M, Castelao, E, Vandeleur, C, Gholam-Rezaee, M, and Aubry, J
Published: 2013

20. Mental disorders in offspring of parents with bipolar and major depressive disorders: RC6

Author: Vandeleur, C, Rothen, S, Gholam-Rezaee, M, Castelao, E, Vidal, S, Favre, S, Ferrero, F, Halfon, O, Fumeaux, P, Merikangas, KR, Aubry, JM, and Preisig, M
Published: 2011

21. Associations of Personality Traits With Chronic Low-Grade Inflammation in a Swiss Community Sample

Author: Wagner, E.N., Ajdacic-Gross, V., Strippoli, M.F., Gholam-Rezaee, M., Glaus, J., Vandeleur, C., Castelao, E., Vollenweider, P., Preisig, M., von Känel, R., University of Zurich, and Wagner, En-Young N
Subjects: Psychiatry, NEO-FFI-R, cardiovascular risk factors, chronic inflammation, Psychiatry and Mental health, C-reactive protein, inflammatory biomarkers, personality traits (big five), 610 Medicine & health, 2738 Psychiatry and Mental Health, 10057 Klinik für Konsiliarpsychiatrie und Psychosomatik, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, Original Research
Abstract: Objective: Among the major dimensions of personality, high Neuroticism and low Conscientiousness have frequently been linked to worse health-related behaviors and poor health outcomes. However, studies on the association between personality traits and biomarkers of chronic low-grade inflammation reflecting increased morbidity and mortality risk are sparse; therefore, the aim of this study was to explore this association. Methods: A population-based Swiss sample of 2,182 persons (40-82 years, 42% men) completed a comprehensive personality questionnaire (NEO Five-Factor Inventory-Revised). Circulating levels of inflammatory markers, including C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and levels of the "cardioprotective" adipo(cyto)kine adiponectin were also determined. Analyses controlled for sociodemographic factors, traditional cardiovascular risk factors and lifetime psychiatric disorders using a validated semi-structured psychiatric interview. The role of gender as a moderator of the personality-inflammation link was additionally explored. Results: Controlling for all covariates, higher Extraversion (β = 0.092, 95%CI 0.004-0.180) was positively associated with higher IL-6 levels, and higher Conscientiousness (β = -0.095, 95%CI -0.180-[-0.009]) were significantly associated with lower IL-6 levels (all p-values < 0.05). Neuroticism and Agreeableness showed no significant association with any inflammatory biomarker. The associations between personality traits and inflammatory markers were not moderated by gender. Conclusions: Conscientiousness seems to be inversely related to chronic low-grade inflammation as measured by IL-6 levels, compatible with protection from the cardiovascular risk. The opposite may apply to Extraversion. Further research is needed to better understand the underlying mechanisms and their impact for health outcomes in the community.
Published: 2019

22. Identification of common genetic risk variants for autism spectrum disorder

Author: Grove, J., Ripke, S., Als, T.D., Mattheisen, M., Walters, R.K., Won, H., Pallesen, J., Agerbo, E., Andreassen, O.A., Anney, R., Awashti, S., Belliveau, R., Bettella, F., Buxbaum, J.D., Bybjerg-Grauholm, J., Baekvad-Hansen, M., Cerrato, F., Chambert, K., Christensen, J.H., Churchhouse, C., Dellenvall, K., Demontis, D., Rubeis, S. de, Devlin, B., Djurovic, S., Dumont, A.L., Goldstein, J.I., Hansen, C.S., Hauberg, M.E., Hollegaard, M.V., Hope, S., Howrigan, D.P., Huang, H., Hultman, C.M., Klei, L., Maller, J., Martin, J., Martin, A.R., Moran, J.L., Nyegaard, M., Naeland, T., Palmer, D.S., Palotie, A., Pedersen, C.B., Pedersen, M.G., dPoterba, T., Poulsen, J.B., St Pourcain, B., Qvist, P., Rehnstrom, K., Reichenberg, A., Reichert, J., Robinson, E.B., Roeder, K., Roussos, P., Saemundsen, E., Sandin, S., Satterstrom, F.K., Smith, G.D., Stefansson, H., Steinberg, S., Stevens, C.R., Sullivan, P.F., Turley, P., Walters, G.B., Xu, X.Y., Stefansson, K., Geschwind, D.H., Nordentoft, M., Hougaard, D.M., Werge, T., Mors, O., Mortensen, P.B., Neale, B.M., Daly, M.J., Borglum, A.D., Wray, N.R., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Air, T.M., Andlauer, T.F.M., Bacanu, S.A., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenschon, H.N., Cai, N., Castelao, E., Clarke, T.K., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Hall, L.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Ising, M., Jansen, R., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Li, Y., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y.P., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.S., Yang, J., Zhang, F.T., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Muller-Myhsok, B., Nothen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Tiemeier, H., Uher, R., Volzke, H., Weissman, M.M., Lewis, C.M., Levinson, D.F., Breen, G., Agee, M., Alipanahi, B., Auton, A., Bell, R.K., Bryc, K., Elson, S.L., Fontanillas, P., Furlotte, N.A., Hromatka, B.S., Huber, K.E., Kleinman, A., Litterman, N.K., McIntyre, M.H., Mountain, J.L., Noblin, E.S., Northover, C.A.M., Pitts, S.J., Sathirapongsasuti, J.F., Sazonova, O.V., Shelton, J.F., Shringarpure, S., Tung, J.Y., Vacic, V., Wilson, C.H., Psychiat Genomics Consortium, BUPGEN, 23andMe Re, Biological Psychology, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Adult Psychiatry, Psychiatry, Human genetics, Amsterdam Reproduction & Development (AR&D), VU University medical center, APH - Digital Health, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Me Research Team, Epidemiology, and Child and Adolescent Psychiatry / Psychology
Subjects: Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, Autism Spectrum Disorder, Denmark, LD SCORE REGRESSION, LOCI, Genome-wide association study, DE-NOVO, 0302 clinical medicine, Polymorphism (computer science), Risk Factors, SYNAPTIC PLASTICITY, CELL-SURFACE, Child, Genetics, 0303 health sciences, HERITABILITY, Genetic Predisposition to Disease/genetics, 1184 Genetics, developmental biology, physiology, Polymorphism, Single Nucleotide/genetics, Phenotype, 3. Good health, Schizophrenia, Autism spectrum disorder, Child, Preschool, Genome-Wide Association Study/methods, Female, SIMONS SIMPLEX COLLECTION, Adolescent, Biology, NEURITE OUTGROWTH, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, 03 medical and health sciences, mental disorders, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, SDG 2 - Zero Hunger, Multifactorial Inheritance/genetics, METAANALYSIS, 030304 developmental biology, Case-control study, Heritability, medicine.disease, Autism Spectrum Disorder/genetics, Case-Control Studies, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Published in final edited form as: Nat Genet. 2019 March ; 51(3): 431–444. doi:10.1038/s41588-019-0344-8., Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture, we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis and establish that GWAS performed at scale will be much more productive in the near term in ASD., The iPSYCH project is funded by the Lundbeck Foundation (grant numbers R102-A9118 and R155-2014-1724) and the universities and university hospitals of Aarhus and Copenhagen. Genotyping of iPSYCH and PGC samples was supported by grants from the Lundbeck Foundation, the Stanley Foundation, the Simons Foundation (SFARI 311789 to MJD), and NIMH (5U01MH094432–02 to MJD). The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514–01 to M O’Donovan and ADB). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). Drs. S De Rubeis and JD Buxbaum were supported by NIH grants MH097849 (to JDB) and MH111661 (to JDB), and by the Seaver Foundation (to SDR and JDB). Dr J Martin was supported by the Wellcome Trust (grant no: 106047). O. Andreassen received funding from Research Council of Norway (#213694, #223273, #248980, #248778), Stiftelsen KG Jebsen and South-East Norway Health Authority. We thank the research participants and employees of 23andMe for making this work possible.
Published: 2019

23. 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, M.J., Clarke, T.K., MacIntyre, D.J., Milburn, K., Navrady, L., Hayward, C., McIntosh, A.M., Thomson, P.A., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Agerbo, E., Air, T.M., Andlauer, T.F.M., Bacanu, S.A., Baekvad-Hansen, M., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenscon, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Coleman, J.R.I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Rawford, G.E.C., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Foo, J.C., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., Macintyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y.P., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., Metspalu, A., Mors, O., Mortensen, P.B., Muller-Myhsok, B., Nordentoft, M., Nothen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.S.D., Sullivan, P.F., Generation Scotland, and Psychiat Genomics Consortium
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 x 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 x 10(-9); total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 x 10(-8); dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 x 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 x 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 x 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

24. Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Author: Foo, J.C., Streit, F., Frank, J., Witt, S.H., Treutlein, J., Baune, B.T., Moebus, S., Jockel, K.H., Forstner, A.J., Nothen, M.M., Rietschel, M., Sartorius, A., Kranaster, L., Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, T.F.M., Bacanu, S.A., Baekvad-Hansen, M., Beekman, A.T.F., Bigdeli, T.B., Binder, E.B., Blackwood, D.H.R., Bryois, J., Buttenschon, 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., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, F.F.H., Finucane, H.K., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Krogh, J., Kutalik, Z., Li, Y.H., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J.X., Shyn, S.I., Sigurdsson, E., Sinnamon, G.C.B., Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Auwera, S. van der, Hemert, A.M. van, Viktorin, A., Visscher, P.M., Wang, Y., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H.L.S., Yang, J., Zhang, F.T., Arolt, V., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., Geus, E.J.C. de, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.Q.S., Lucae, S., Madden, P.A.F., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, B.W.J.H., Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Voelzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Borglum, A.D., Sullivan, P.F., and Major Depressive Disorder Worki
Subjects: treatment-resistance, polygenic risk scores, depression, major depression, electroconvulsive therapy
Abstract: Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistantdepression; disorder severity and unfavorable treatment outcomes are shown to be influencedby an increased genetic burden for major depression (MD). Here, we tested whether ECT assign-ment and response/nonresponse are associated with an increased genetic burden for majordepression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressiveepisode underwent ECT. MD-PRS were calculated for these inpatients and a separatepopulation-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on sum-mary 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 statusbetween ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higherMD-PRS. MD-PRS in population-based depression self-reporters were intermediate betweenECT 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 indi-cate that ECT cohorts show an increased genetic burden for MD and are consistent with thehypothesis that treatment-resistant MD patients represent a subgroup with an increased geneticrisk for MD. Larger samples are needed to better substantiate these findings.
Published: 2019

25. Erratum: Meta-analysis of genome-wide association studies of anxiety disorders

Author: Otowa, T, Hek, K, Lee, M, Byrne, E M, Mirza, S S, Nivard, M G, Bigdeli, T, Aggen, S H, Adkins, D, Wolen, A, Fanous, A, Keller, M C, Castelao, E, Kutalik, Z, der Auwera, S V, Homuth, G, Nauck, M, Teumer, A, Milaneschi, Y, Hottenga, J-J, Direk, N, Hofman, A, Uitterlinden, A, Mulder, C L, Henders, A K, Medland, S E, Gordon, S, Heath, A C, Madden, P A F, Pergadia, M L, van der Most, P J, Nolte, I M, van Oort, F V A, Hartman, C A, Oldehinkel, A J, Preisig, M, Grabe, H J, Middeldorp, C M, Penninx, B W J H, Boomsma, D, Martin, N G, Montgomery, G, Maher, B S, van den Oord, E J, Wray, N R, Tiemeier, H, and Hettema, J M
Published: 2016
Full Text: View/download PDF

26. 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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27. 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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28. 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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29. 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

30. 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

31. 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

32. Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Author: de Jong, S, Diniz, MJA, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, SA, Bækvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschøn, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, TK, 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, 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, JJ, 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, de Jong, S, Diniz, MJA, Saloma, A, Gadelha, A, Santoro, ML, Ota, VK, Noto, C, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, SA, Bækvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschøn, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, TK, 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, 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, JJ, 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, and Painter, JN
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

33. The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders

Author: Chang, H, Hoshina, N, Zhang, C, Ma, Y, Cao, H, Wang, Y, Wu, DD, Bergen, SE, Landén, M, Hultman, CM, Preisig, M, Kutalik, Z, Castelao, E, Grigoroiu-Serbanescu, M, Forstner, AJ, Strohmaier, J, Hecker, J, Schulze, TG, Müller-Myhsok, B, Reif, A, Mitchell, PB, Martin, NG, Schofield, PR, Cichon, S, Nöthen, MM, Walter, H, Erk, S, Heinz, A, Amin, N, Van Duijn, CM, Meyer-Lindenberg, A, Tost, H, Xiao, X, Yamamoto, T, Rietschel, M, Li, M, Backlund, L, Frisén, L, Lavebratt, C, Schalling, M, Ösby, U, Mühleisen, TW, Leber, M, Degenhardt, F, Treutlein, J, Mattheisen, M, Maaser, A, Meier, S, Herms, S, Hoffmann, P, Lacour, A, Witt, SH, Streit, F, Lucae, S, Maier, W, Schwarz, M, Vedder, H, Kammerer-Ciernioch, J, Pfennig, A, Bauer, M, Hautzinger, M, Wright, A, Fullerton, JM, Montgomery, GW, Medland, SE, Gordon, SD, Becker, T, Schumacher, J, Propping, P, Chang, H, Hoshina, N, Zhang, C, Ma, Y, Cao, H, Wang, Y, Wu, DD, Bergen, SE, Landén, M, Hultman, CM, Preisig, M, Kutalik, Z, Castelao, E, Grigoroiu-Serbanescu, M, Forstner, AJ, Strohmaier, J, Hecker, J, Schulze, TG, Müller-Myhsok, B, Reif, A, Mitchell, PB, Martin, NG, Schofield, PR, Cichon, S, Nöthen, MM, Walter, H, Erk, S, Heinz, A, Amin, N, Van Duijn, CM, Meyer-Lindenberg, A, Tost, H, Xiao, X, Yamamoto, T, Rietschel, M, Li, M, Backlund, L, Frisén, L, Lavebratt, C, Schalling, M, Ösby, U, Mühleisen, TW, Leber, M, Degenhardt, F, Treutlein, J, Mattheisen, M, Maaser, A, Meier, S, Herms, S, Hoffmann, P, Lacour, A, Witt, SH, Streit, F, Lucae, S, Maier, W, Schwarz, M, Vedder, H, Kammerer-Ciernioch, J, Pfennig, A, Bauer, M, Hautzinger, M, Wright, A, Fullerton, JM, Montgomery, GW, Medland, SE, Gordon, SD, Becker, T, Schumacher, J, and Propping, P
Abstract: Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
Published: 2018

34. 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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35. The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders

Author: Chang, H., Hoshina, N., Zhang, C., Ma, Y., Cao, H., Wang, Y., Wu, D.-D., Bergen, S.E. (Sarah), Landén, M. (Mikael), Hultman, C.M. (Christina), Preisig, M. (Martin), Kutalik, Z. (Zoltán), Castelao, E., Grigoroiu-Serbanescu, M., Forstner, A.J. (Andreas), Strohmaier, J., Hecker, J., Schulze, T.G. (Thomas), Müller-Myhsok, B. (B.), Reif, A., Mitchell, P.B., Martin, N.G. (Nicholas), Schofield, P.R., Cichon, S. (Sven), Nöthen, M.M. (Markus), Walter, H.J. (Henrik), Erk, S., A. Heinz, Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Meyer-Lindenberg, A., Tost, H., Xiao, X., Yamamoto, T., Rietschel, M. (Marcella), Li, M. (M.), Chang, H., Hoshina, N., Zhang, C., Ma, Y., Cao, H., Wang, Y., Wu, D.-D., Bergen, S.E. (Sarah), Landén, M. (Mikael), Hultman, C.M. (Christina), Preisig, M. (Martin), Kutalik, Z. (Zoltán), Castelao, E., Grigoroiu-Serbanescu, M., Forstner, A.J. (Andreas), Strohmaier, J., Hecker, J., Schulze, T.G. (Thomas), Müller-Myhsok, B. (B.), Reif, A., Mitchell, P.B., Martin, N.G. (Nicholas), Schofield, P.R., Cichon, S. (Sven), Nöthen, M.M. (Markus), Walter, H.J. (Henrik), Erk, S., A. Heinz, Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Meyer-Lindenberg, A., Tost, H., Xiao, X., Yamamoto, T., Rietschel, M. (Marcella), and Li, M. (M.)
Abstract: Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
Published: 2018
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36. Color in concentrated milk proteins with high sucrose as affected by glucose replacement

Author: Pauletti, M.S., Matta, E.J., Castelao,E., and Rozycki, D.S.
Subjects: Milk proteins -- Research, Food research -- Observations, Business, Food/cooking/nutrition
Abstract: Brown color develops when heating milk at high temperatures, with maillard and caramelization reactions the main factors in color development. Color differences can be expressed by the Kubella-Munk index (K/S) and it is necessary to the reflectivity value R. To determine the influence of sucrose replacement by glucose on color of concentrated milk, an indirect estimation of R is proposed using equations derived from Kubella-Munk theory. The Self-Backing Reflectance Transformation (SBRT) procedure was suitable for evaluating the self-backing reflectance in small samples. The Kubelka-Munk Index is suitable for quality control of darkened products.
Published: 1999

37. Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders

Author: Xiao, X. (Xiao), Wang, L. (Lu), Wang, C. (Chuang), Yuan, T.-F. (Ti-Fei), Zhou, D. (Dongsheng), Zheng, F. (Fanfan), Li, L. (Lingyi), Grigoroiu-Serbanescu, M. (Maria), Ikeda, M. (Masashi), Iwata, N. (Nakao), Takahashi, A. (Atsushi), Kamatani, Y. (Yoichiro), Kubo, M. (Michiaki), Preisig, M. (Martin), Kutalik, Z. (Zoltán), Castelao, E. (Enrique), Pistis, G. (Giorgio), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Forstner, A.J. (Andreas), Strohmaier, J., Hecker, J. (Julian), Schulze, T.G. (Thomas), Müller-Myhsok, B. (B.), Reif, A. (Andreas), Mitchell, P.B. (Philip B.), Martin, N.G. (Nicholas G.), Schofield, C.J. (Christopher), Cichon, S. (Sven), Nöthen, M.M. (Markus), Chang, H. (Hong), Luo, X.-J. (X.), Fang, Y. (Yiru), Yao, Y.-G. (Yong-Gang), Zhang, C. (Chen), Rietschel, M. (Marcella), Li, M. (Ming), Xiao, X. (Xiao), Wang, L. (Lu), Wang, C. (Chuang), Yuan, T.-F. (Ti-Fei), Zhou, D. (Dongsheng), Zheng, F. (Fanfan), Li, L. (Lingyi), Grigoroiu-Serbanescu, M. (Maria), Ikeda, M. (Masashi), Iwata, N. (Nakao), Takahashi, A. (Atsushi), Kamatani, Y. (Yoichiro), Kubo, M. (Michiaki), Preisig, M. (Martin), Kutalik, Z. (Zoltán), Castelao, E. (Enrique), Pistis, G. (Giorgio), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Forstner, A.J. (Andreas), Strohmaier, J., Hecker, J. (Julian), Schulze, T.G. (Thomas), Müller-Myhsok, B. (B.), Reif, A. (Andreas), Mitchell, P.B. (Philip B.), Martin, N.G. (Nicholas G.), Schofield, C.J. (Christopher), Cichon, S. (Sven), Nöthen, M.M. (Markus), Chang, H. (Hong), Luo, X.-J. (X.), Fang, Y. (Yiru), Yao, Y.-G. (Yong-Gang), Zhang, C. (Chen), Rietschel, M. (Marcella), and Li, M. (Ming)
Abstract: Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.
Published: 2017
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38. Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders

Author: Xiao, X, Wang, L, Wang, C, Yuan, TF, Zhou, D, Zheng, F, Li, L, Grigoroiu-Serbanescu, M, Ikeda, M, Iwata, N, Takahashi, A, Kamatani, Y, Kubo, M, Preisig, M, Kutalik, Z, Castelao, E, Pistis, G, Amin, N, Van Duijn, CM, Forstner, AJ, Strohmaier, J, Hecker, J, Schulze, TG, Müller-Myhsok, B, Reif, A, Mitchell, PB, Martin, NG, Schofield, PR, Cichon, S, Nöthen, MM, Chang, H, Luo, XJ, Fang, Y, Yao, YG, Zhang, C, Rietschel, M, Li, M, Xiao, X, Wang, L, Wang, C, Yuan, TF, Zhou, D, Zheng, F, Li, L, Grigoroiu-Serbanescu, M, Ikeda, M, Iwata, N, Takahashi, A, Kamatani, Y, Kubo, M, Preisig, M, Kutalik, Z, Castelao, E, Pistis, G, Amin, N, Van Duijn, CM, Forstner, AJ, Strohmaier, J, Hecker, J, Schulze, TG, Müller-Myhsok, B, Reif, A, Mitchell, PB, Martin, NG, Schofield, PR, Cichon, S, Nöthen, MM, Chang, H, Luo, XJ, Fang, Y, Yao, YG, Zhang, C, Rietschel, M, and Li, M
Abstract: Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.
Published: 2017

39. Genome-wide Regional Heritability Mapping Identifies a Locus Within the TOX2 Gene Associated With Major Depressive Disorder

Author: Zeng, Y, Navarro, P, Shirali, M, Howard, DM, Adams, MJ, Hall, LS, Clarke, T-K, Thomson, PA, Smith, BH, Murray, A, Padmanabhan, S, Hayward, C, Boutin, T, MacIntyre, DJ, Lewis, CM, Wray, NR, Mehta, D, Penninx, BWJH, Milaneschi, Y, Baune, BT, Air, T, Hottenga, J-J, Mbarek, H, Castelao, E, Pistis, G, Schulze, TG, Streit, F, Forstner, AJ, Byrne, EM, Martin, NG, Breen, G, Mueller-Myhsok, B, Lucae, S, Kloiber, S, Domenici, E, Deary, IJ, Porteous, DJ, Haley, CS, McIntosh, AM, Zeng, Y, Navarro, P, Shirali, M, Howard, DM, Adams, MJ, Hall, LS, Clarke, T-K, Thomson, PA, Smith, BH, Murray, A, Padmanabhan, S, Hayward, C, Boutin, T, MacIntyre, DJ, Lewis, CM, Wray, NR, Mehta, D, Penninx, BWJH, Milaneschi, Y, Baune, BT, Air, T, Hottenga, J-J, Mbarek, H, Castelao, E, Pistis, G, Schulze, TG, Streit, F, Forstner, AJ, Byrne, EM, Martin, NG, Breen, G, Mueller-Myhsok, B, Lucae, S, Kloiber, S, Domenici, E, Deary, IJ, Porteous, DJ, Haley, CS, and McIntosh, AM
Abstract: BACKGROUND: Major depressive disorder (MDD) is the second largest cause of global disease burden. It has an estimated heritability of 37%, but published genome-wide association studies have so far identified few risk loci. Haplotype-block-based regional heritability mapping (HRHM) estimates the localized genetic variance explained by common variants within haplotype blocks, integrating the effects of multiple variants, and may be more powerful for identifying MDD-associated genomic regions. METHODS: We applied HRHM to Generation Scotland: The Scottish Family Health Study, a large family- and population-based Scottish cohort (N = 19,896). Single-single nucleotide polymorphism (SNP) and haplotype-based association tests were used to localize the association signal within the regions identified by HRHM. Functional prediction was used to investigate the effect of MDD-associated SNPs within the regions. RESULTS: A haplotype block across a 24-kb region within the TOX2 gene reached genome-wide significance in HRHM. Single-SNP- and haplotype-based association tests demonstrated that five of nine genotyped SNPs and two haplotypes within this block were significantly associated with MDD. The expression of TOX2 and a brain-specific long noncoding RNA RP1-269M15.3 in frontal cortex and nucleus accumbens basal ganglia, respectively, were significantly regulated by MDD-associated SNPs within this region. Both the regional heritability and single-SNP associations within this block were replicated in the UK-Ireland group of the most recent release of the Psychiatric Genomics Consortium (PGC), the PGC2-MDD (Major Depression Dataset). The SNP association was also replicated in a depressive symptom sample that shares some individuals with the PGC2-MDD. CONCLUSIONS: This study highlights the value of HRHM for MDD and provides an important target within TOX2 for further functional studies.
Published: 2017

40. Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study

Author: Glaus, J., primary, von Känel, R., additional, Lasserre, A. M., additional, Strippoli, M.-P. F., additional, Vandeleur, C. L., additional, Castelao, E., additional, Gholam-Rezaee, M., additional, Marangoni, C., additional, Wagner, E.-Y. N., additional, Marques-Vidal, P., additional, Waeber, G., additional, Vollenweider, P., additional, Preisig, M., additional, and Merikangas, K. R., additional
Published: 2017
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41. Hypomania Checklist-32 - cross-validation of shorter versions screening for bipolar disorders in an epidemiological study

Author: Meyer, T. D., primary, Castelao, E., additional, Gholamrezaee, M., additional, Angst, J., additional, and Preisig, M., additional
Published: 2017
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42. Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance

Author: Li, M, Luo, XJ, Landén, M, Bergen, SE, Hultman, CM, Li, X, Zhang, W, Yao, YG, Zhang, C, Liu, J, Mattheisen, M, Cichon, S, Mühleisen, TW, Degenhardt, FA, Nöthen, MM, Schulze, TG, Grigoroiu-Serbanescu, M, Li, H, Fuller, CK, Chen, C, Dong, Q, Jamain, S, Leboyer, M, Bellivier, F, Etain, B, Kahn, JP, Henry, C, Preisig, M, Kutalik, Z, Castelao, E, Wright, A, Mitchell, PB, Fullerton, JM, Schofield, PR, Montgomery, GW, Medland, SE, Gordon, SD, Martin, NG, Rietschel, M, Liu, C, Kleinman, JE, Hyde, TM, Weinberger, DR, Su, B, Li, M, Luo, XJ, Landén, M, Bergen, SE, Hultman, CM, Li, X, Zhang, W, Yao, YG, Zhang, C, Liu, J, Mattheisen, M, Cichon, S, Mühleisen, TW, Degenhardt, FA, Nöthen, MM, Schulze, TG, Grigoroiu-Serbanescu, M, Li, H, Fuller, CK, Chen, C, Dong, Q, Jamain, S, Leboyer, M, Bellivier, F, Etain, B, Kahn, JP, Henry, C, Preisig, M, Kutalik, Z, Castelao, E, Wright, A, Mitchell, PB, Fullerton, JM, Schofield, PR, Montgomery, GW, Medland, SE, Gordon, SD, Martin, NG, Rietschel, M, Liu, C, Kleinman, JE, Hyde, TM, Weinberger, DR, and Su, B
Abstract: Background Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. Aims We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. Method To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals. Results Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.8561075). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.5461078). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. Conclusions Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
Published: 2016

43. Erste Validierung eines neu entwickelten Fragesbogens zur Erfassung von Angst, Vertrauen und Zufriedenheit bei verschiedenen Behandlungsmethoden in der Kinderunfallchirurgie

Author: Sehmisch, S, Carnehl, F, Fernandez Castelao, E, Ammon, JC, August, F, Dresing, K, Sehmisch, S, Carnehl, F, Fernandez Castelao, E, Ammon, JC, August, F, and Dresing, K
Published: 2016

44. Sex-related and non-sex-related comorbidity subtypes of tic disorders: a latent class approach

Author: Rodgers, S, Müller, M, Kawohl, W, Knöpfli, D, Rössler, W, Castelao, E, Preisig, M, Ajdacic-Gross, V, University of Zurich, and Rodgers, S
Subjects: 2728 Neurology (clinical), 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, 2808 Neurology, 610 Medicine & health
Published: 2014

45. Prospective associations of depression subtypes with cardio-metabolic risk factors in the general population

Author: Lasserre, A M, primary, Strippoli, M-P F, additional, Glaus, J, additional, Gholam-Rezaee, M, additional, Vandeleur, C L, additional, Castelao, E, additional, Marques-Vidal, P, additional, Waeber, G, additional, Vollenweider, P, additional, and Preisig, M, additional
Published: 2016
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46. Cortisol, life events and cognition in non-demented subjects: A population-based study

Author: Ouanes, S., primary, Castelao, E., additional, Von Gunten, A., additional, Preisig, M., additional, and Popp, J., additional
Published: 2016
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47. Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression

Author: Smalheiser, NR, Delacretaz, A, Preisig, M, Vandenberghe, F, Morgui, NS, Quteineh, L, Choong, E, Gholam-Rezaee, M, Kutalik, Z, Magistretti, P, Aubry, J-M, von Gunten, A, Castelao, E, Vollenweider, P, Waeber, G, Conus, P, Eap, CB, Smalheiser, NR, Delacretaz, A, Preisig, M, Vandenberghe, F, Morgui, NS, Quteineh, L, Choong, E, Gholam-Rezaee, M, Kutalik, Z, Magistretti, P, Aubry, J-M, von Gunten, A, Castelao, E, Vollenweider, P, Waeber, G, Conus, P, and Eap, CB
Abstract: Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.
Published: 2015

48. Association between sleep characteristics and mild cognitive impairment: The HypnoLaus/Psycholaus study

Author: Haba-Rubio, J., primary, Tobback, N., additional, Andries, D., additional, Preisig, M., additional, Castelao, E., additional, Tafti, M., additional, Heinzer, R., additional, and Popp, J., additional
Published: 2015
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49. Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study.

Author: Glaus, J., von Känel, R., Lasserre, A. M., Strippoli, M.-P. F., Vandeleur, C. L., Castelao, E., Gholam-Rezaee, M., Marangoni, C., Wagner, E.-Y. N., Marques-Vidal, P., Waeber, G., Vollenweider, P., Preisig, M., and Merikangas, K. R.
Subjects: AFFECTIVE disorders, BIOMARKERS, C-reactive protein, CARDIOVASCULAR diseases risk factors, CONFIDENCE intervals, MENTAL depression, INFLAMMATION, INTERLEUKINS, INTERVIEWING, LONGITUDINAL method, BIPOLAR disorder, RESEARCH methodology, TUMOR necrosis factors, LOGISTIC regression analysis, MULTIPLE regression analysis, POPULATION-based case control
Abstract: Background: There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)- α and high sensitivity C-reactive protein (hsCRP) with mood disorders. Methods: The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models. Results: Current combined MDD [ β = 0.29, 95% confidence interval (CI) 0.03–0.55] and current atypical MDD (β = 0.32, 95% CI 0.10–0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up. Conclusions: The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated. [ABSTRACT FROM AUTHOR]
Published: 2018
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50. Associations of serum uric acid and SLC2A9 variant with depressive and anxiety disorders: a population-based study

Author: Lyngdoh, T., Bochud, M., Glaus, J., Castelao, E., Waeber, G., Vollenweider, P., Preisig, M., Lyngdoh, T., Bochud, M., Glaus, J., Castelao, E., Waeber, G., Vollenweider, P., and Preisig, M.
Abstract: Background: Limited information exists regarding the association between serum uric acid (SUA) and psychiatric disorders. We explored the relationship between SUA and subtypes of major depressive disorder (MDD) and specific anxiety disorders. Additionally, we examined the association of SLC2A9 rs6855911 variant with anxiety disorders. Methods: We conducted a cross-sectional analysis on 3,716 individuals aged 35-66 years previously selected for the population-based CoLaus survey and who agreed to undergo further psychiatric evaluation. SUA was measured using uricase-PAP method. The French translation of the semi-structured Diagnostic Interview for Genetic Studies was used to establish lifetime and current diagnoses of depression and anxiety disorders according to the DSM-IV criteria. Results: Men reported significantly higher levels of SUA compared to women (357±74 μmol/L vs. 263±64 μmol/L). The prevalence of lifetime and current MDD was 44% and 18% respectively while the corresponding estimates for any anxiety disorders were 18% and 10% respectively. A quadratic hockey-stick shaped curve explained the relationship between SUA and social phobia better than a linear trend. However, with regards to the other specific anxiety disorders and other subtypes of MDD, there was no consistent pattern of association. Further analyses using SLC2A9 rs6855911 variant, known to be strongly associated with SUA, supported the quadratic relationship observed between SUA phenotype and social phobia. Conclusions: A quadratic relationship between SUA and social phobia was observed consistent with a protective effect of moderately elevated SUA on social phobia, which disappears at higher concentrations. Further studies are needed to confirm our observations.
Published: 2013

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