Search

Your search keyword '"Ryu E"' showing total 11 results
Start Over Author "Ryu E" Topic bipolar disorder
11 results on '"Ryu E"'

1. Expression of telomerase reverse transcriptase positively correlates with duration of lithium treatment in bipolar disorder.

Author

Lundberg M, Biernacka JM, Lavebratt C, Druliner B, Ryu E, Geske J, Colby C, Boardman L, Frye M, and Schalling M

Subjects
Adult, Aging genetics, Bipolar Disorder blood, Cellular Senescence drug effects, Female, Humans, Lithium Compounds pharmacology, Male, Middle Aged, Mitochondria metabolism, Oxidative Stress drug effects, Polymorphism, Single Nucleotide genetics, Real-Time Polymerase Chain Reaction, Telomerase drug effects, Telomerase genetics, Telomere drug effects, Telomere genetics, Telomere metabolism, Telomere Homeostasis genetics, Telomere Shortening drug effects, Telomere Shortening genetics, Aging metabolism, Antimanic Agents therapeutic use, Bipolar Disorder drug therapy, Bipolar Disorder genetics, Cellular Senescence genetics, Lithium therapeutic use, Lithium Compounds therapeutic use, Telomerase metabolism
Abstract

Bipolar disorder (BD) may be associated with accelerated cellular aging. However, previous studies on telomere length (TL), an important biomarker of cellular aging, have yielded mixed results in BD. We aimed to evaluate the hypothesis that BD is associated with telomere shortening and whether this is counteracted by long-term lithium treatment. We also sought to determine whether long-term lithium treatment is associated with increased expression of telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. We determined TL and TERT expression in 100 BD I patients and 100 healthy controls. We also genotyped three single nucleotide polymorphisms associated with TL. TERT expression was significantly increased in BD I patients currently on lithium treatment. TERT expression was also significantly positively correlated with duration of lithium treatment in patients treated for 24 months or more. However, we did not find any significant effect of lithium treatment on TL. Neither did we find significant differences in TL between BD patients and controls. We suggest that long-term lithium treatment is associated with an increase in the expression of TERT. We hypothesize that an increase in TERT expression may contribute to lithium's mood stabilizing and neuroprotective properties by improving mitochondrial function and decreasing oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Published
2020
Full Text
View/download PDF

2. The impact of sample processing on inflammatory markers in serum: Lessons learned.

Author

Pan AY, Ryu E, Geske JR, Zhou XY, McElroy SL, Cicek MS, Frye MA, Biernacka JM, and Andreazza AC

Subjects
Biomarkers, Case-Control Studies, Humans, Inflammation, Specimen Handling, Bipolar Disorder metabolism, Cytokines metabolism
Abstract

Objectives: To investigate the effect of sample handling on inflammatory cytokines in serum and highlight challenges with using samples pre-collected from biobanks for biomarker research. Methods: Cytokine concentrations (IL-1β, IL-2, IL-6, IL-8, IL-10, TNFα, and IFNγ) were measured in serum samples of 205 patients with bipoldar disorder (BD) from the Mayo Clinic Bipolar Disorder Biobank and 205 non-psychiatric controls from the Mayo Clinic Biobank. As cytokine concentrations varied by recruitment site, post-hoc models were used to test the effect of clinical variables and pre-processing time on cytokines. To evaluate the effect of pre-processing time experimentally, cytokines were assayed in serum and plasma from 6 healthy volunteers processed at different time points. Results: Cytokine levels were significantly higher in the BD group. However, both cytokine levels and pre-processing times differed by recruitment site, and post-hoc analyses revealed that pre-processing time was significantly associated with several cytokines. An experiment using samples from healthy volunteers confirmed that concentrations for most cytokines increased with longer pre-processing times. Conclusions: Delays in processing influence cytokine concentrations in blood samples. Given the increasing use of biobanks in research, this study highlights the need to carefully evaluate sample collection and handling methods when designing biomarker studies.

Published
2020
Full Text
View/download PDF

3. Genome-wide association study identifies 30 loci associated with bipolar disorder.

Author

Stahl EA, Breen G, Forstner AJ, McQuillin A, Ripke S, Trubetskoy V, Mattheisen M, Wang Y, Coleman JRI, Gaspar HA, de Leeuw CA, Steinberg S, Pavlides JMW, Trzaskowski M, Byrne EM, Pers TH, Holmans PA, Richards AL, Abbott L, Agerbo E, Akil H, Albani D, Alliey-Rodriguez N, Als TD, Anjorin A, Antilla V, Awasthi S, Badner JA, Bækvad-Hansen M, Barchas JD, Bass N, Bauer M, Belliveau R, Bergen SE, Pedersen CB, Bøen E, Boks MP, Boocock J, Budde M, Bunney W, Burmeister M, Bybjerg-Grauholm J, Byerley W, Casas M, Cerrato F, Cervantes P, Chambert K, Charney AW, Chen D, Churchhouse C, Clarke TK, Coryell W, Craig DW, Cruceanu C, Curtis D, Czerski PM, Dale AM, de Jong S, Degenhardt F, Del-Favero J, DePaulo JR, Djurovic S, Dobbyn AL, Dumont A, Elvsåshagen T, Escott-Price V, Fan CC, Fischer SB, Flickinger M, Foroud TM, Forty L, Frank J, Fraser C, Freimer NB, Frisén L, Gade K, Gage D, Garnham J, Giambartolomei C, Pedersen MG, Goldstein J, Gordon SD, Gordon-Smith K, Green EK, Green MJ, Greenwood TA, Grove J, Guan W, Guzman-Parra J, Hamshere ML, Hautzinger M, Heilbronner U, Herms S, Hipolito M, Hoffmann P, Holland D, Huckins L, Jamain S, Johnson JS, Juréus A, Kandaswamy R, Karlsson R, Kennedy JL, Kittel-Schneider S, Knowles JA, Kogevinas M, Koller AC, Kupka R, Lavebratt C, Lawrence J, Lawson WB, Leber M, Lee PH, Levy SE, Li JZ, Liu C, Lucae S, Maaser A, MacIntyre DJ, Mahon PB, Maier W, Martinsson L, McCarroll S, McGuffin P, McInnis MG, McKay JD, Medeiros H, Medland SE, Meng F, Milani L, Montgomery GW, Morris DW, Mühleisen TW, Mullins N, Nguyen H, Nievergelt CM, Adolfsson AN, Nwulia EA, O'Donovan C, Loohuis LMO, Ori APS, Oruc L, Ösby U, Perlis RH, Perry A, Pfennig A, Potash JB, Purcell SM, Regeer EJ, Reif A, Reinbold CS, Rice JP, Rivas F, Rivera M, Roussos P, Ruderfer DM, Ryu E, Sánchez-Mora C, Schatzberg AF, Scheftner WA, Schork NJ, Shannon Weickert C, Shehktman T, Shilling PD, Sigurdsson E, Slaney C, Smeland OB, Sobell JL, Søholm Hansen C, Spijker AT, St Clair D, Steffens M, Strauss JS, Streit F, Strohmaier J, Szelinger S, Thompson RC, Thorgeirsson TE, Treutlein J, Vedder H, Wang W, Watson SJ, Weickert TW, Witt SH, Xi S, Xu W, Young AH, Zandi P, Zhang P, Zöllner S, Adolfsson R, Agartz I, Alda M, Backlund L, Baune BT, Bellivier F, Berrettini WH, Biernacka JM, Blackwood DHR, Boehnke M, Børglum AD, Corvin A, Craddock N, Daly MJ, Dannlowski U, Esko T, Etain B, Frye M, Fullerton JM, Gershon ES, Gill M, Goes F, Grigoroiu-Serbanescu M, Hauser J, Hougaard DM, Hultman CM, Jones I, Jones LA, Kahn RS, Kirov G, Landén M, Leboyer M, Lewis CM, Li QS, Lissowska J, Martin NG, Mayoral F, McElroy SL, McIntosh AM, McMahon FJ, Melle I, Metspalu A, Mitchell PB, Morken G, Mors O, Mortensen PB, Müller-Myhsok B, Myers RM, Neale BM, Nimgaonkar V, Nordentoft M, Nöthen MM, O'Donovan MC, Oedegaard KJ, Owen MJ, Paciga SA, Pato C, Pato MT, Posthuma D, Ramos-Quiroga JA, Ribasés M, Rietschel M, Rouleau GA, Schalling M, Schofield PR, Schulze TG, Serretti A, Smoller JW, Stefansson H, Stefansson K, Stordal E, Sullivan PF, Turecki G, Vaaler AE, Vieta E, Vincent JB, Werge T, Nurnberger JI, Wray NR, Di Florio A, Edenberg HJ, Cichon S, Ophoff RA, Scott LJ, Andreassen OA, Kelsoe J, and Sklar P

Subjects
Bipolar Disorder classification, Case-Control Studies, Depressive Disorder, Major genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Psychotic Disorders genetics, Schizophrenia genetics, Systems Biology, Bipolar Disorder genetics, Genetic Loci
Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 -4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10 -8 ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

Published
2019
Full Text
View/download PDF

4. A genome wide association study suggests the association of muskelin with early onset bipolar disorder: Implications for a GABAergic epileptogenic neurogenesis model.

Author

Nassan M, Li Q, Croarkin PE, Chen W, Colby CL, Veldic M, McElroy SL, Jenkins GD, Ryu E, Cunningham JM, Leboyer M, Frye MA, and Biernacka JM

Subjects
Adolescent, Age of Onset, Bipolar Disorder metabolism, Case-Control Studies, Cell Adhesion Molecules metabolism, Child, Child, Preschool, Genetic Markers, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins metabolism, Models, Genetic, Neurogenesis genetics, Phenotype, Receptors, GABA-A metabolism, Young Adult, Bipolar Disorder genetics, Cell Adhesion Molecules genetics, Genetic Predisposition to Disease, Intracellular Signaling Peptides and Proteins genetics, Polymorphism, Single Nucleotide
Abstract

Background: Although multiple genes have been implicated in bipolar disorder (BD), they explain only a small proportion of its heritability. Identifying additional BD risk variants may be impaired by phenotypic heterogeneity, which is usually not taken into account in genome-wide association studies (GWAS). BD with early age at onset is a more homogeneous familial form of the disorder associated with greater symptom severity., Methods: We conducted a GWAS of early-onset BD (onset of mania/hypomania ≤19 years old) in a discovery sample of 419 cases and 1034 controls and a replication sample of 181 cases and 777 controls. These two samples were meta-analyzed, followed by replication of one signal in a third independent sample of 141 cases and 746 controls., Results: No single nucleotide polymorphism (SNP) associations were genome-wide significant in the discovery sample. Of the top 15 SNPs in the discovery analysis, rs114034759 in the muskelin (MKLN1) gene was nominally significant in the replication analysis, and was among the top associations in the meta-analysis (p=2.63E-06, OR=1.9). In the third sample, this SNP was again associated with early-onset BD (p=0.036, OR=1.6). Gene expression analysis showed that the rs114034759 risk allele is associated with decreased hippocampal MKLN1 expression., Limitations: The sample sizes of the early-onset BD subgroups were relatively small., Conclusions: Our results suggest MKLN1 is associated with early-onset BD. MKLN1 regulates cellular trafficking of GABA-A receptors, which is involved in synaptic transmission and plasticity, and is implicated in the mechanism of action of a group of antiepileptic mood stabilizers. These results therefore indicate that GABAergic neurotransmission may be implicated in early-onset BD. We propose that an increase in GABA-A receptors in the hippocampus in BD patients due to lower MKLN1 expression might increase the excitability during the GABA-excited early phase of young neurons, leading to an increased risk of developing a manic/hypomanic episode. Further studies are needed to test this model., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2017
Full Text
View/download PDF

5. Mitochondrial DNA sequence data reveals association of haplogroup U with psychosis in bipolar disorder.

Author

Frye MA, Ryu E, Nassan M, Jenkins GD, Andreazza AC, Evans JM, McElroy SL, Oglesbee D Jr, Highsmith WE, and Biernacka JM

Subjects
Adolescent, Adult, Aged, Bipolar Disorder complications, Cross-Sectional Studies, Electron Transport Complex I genetics, Female, Genetic Association Studies, Humans, Male, Middle Aged, Mitochondrial Proteins genetics, NADH Dehydrogenase genetics, Phenotype, Polymorphism, Single Nucleotide, Psychotic Disorders complications, White People genetics, Young Adult, Bipolar Disorder genetics, Bipolar Disorder psychology, DNA, Mitochondrial, Genetic Predisposition to Disease, Haplotypes, Psychotic Disorders genetics
Abstract

Converging genetic, postmortem gene-expression, cellular, and neuroimaging data implicate mitochondrial dysfunction in bipolar disorder. This study was conducted to investigate whether mitochondrial DNA (mtDNA) haplogroups and single nucleotide variants (SNVs) are associated with sub-phenotypes of bipolar disorder. MtDNA from 224 patients with Bipolar I disorder (BPI) was sequenced, and association of sequence variations with 3 sub-phenotypes (psychosis, rapid cycling, and adolescent illness onset) was evaluated. Gene-level tests were performed to evaluate overall burden of minor alleles for each phenotype. The haplogroup U was associated with a higher risk of psychosis. Secondary analyses of SNVs provided nominal evidence for association of psychosis with variants in the tRNA, ND4 and ND5 genes. The association of psychosis with ND4 (gene that encodes NADH dehydrogenase 4) was further supported by gene-level analysis. Preliminary analysis of mtDNA sequence data suggests a higher risk of psychosis with the U haplogroup and variation in the ND4 gene implicated in electron transport chain energy regulation. Further investigation of the functional consequences of this mtDNA variation is encouraged., (Copyright © 2016. Published by Elsevier Ltd.)

Published
2017
Full Text
View/download PDF

6. Leveraging electronic health records to study pleiotropic effects on bipolar disorder and medical comorbidities.

Author

Prieto ML, Ryu E, Jenkins GD, Batzler A, Nassan MM, Cuellar-Barboza AB, Pathak J, McElroy SL, Frye MA, and Biernacka JM

Subjects
Aged, Aged, 80 and over, Arrhythmias, Cardiac epidemiology, Arrhythmias, Cardiac genetics, Bipolar Disorder epidemiology, Calcium Channels, L-Type genetics, Cardiovascular Diseases epidemiology, Cell Adhesion Molecules genetics, Comorbidity, Electronic Health Records, Female, Genome-Wide Association Study, Headache epidemiology, Headache genetics, Humans, Hypertension epidemiology, Hypertension genetics, Male, Metabolic Diseases epidemiology, Middle Aged, Migraine Disorders epidemiology, Migraine Disorders genetics, Nervous System Diseases epidemiology, Polymorphism, Single Nucleotide, White People, Bipolar Disorder genetics, Cardiovascular Diseases genetics, Genetic Pleiotropy, Metabolic Diseases genetics, Nervous System Diseases genetics
Abstract

Patients with bipolar disorder (BD) have a high prevalence of comorbid medical illness. However, the mechanisms underlying these comorbidities with BD are not well known. Certain genetic variants may have pleiotropic effects, increasing the risk of BD and other medical illnesses simultaneously. In this study, we evaluated the association of BD-susceptibility genetic variants with various medical conditions that tend to co-exist with BD, using electronic health records (EHR) data linked to genome-wide single-nucleotide polymorphism (SNP) data. Data from 7316 Caucasian subjects were used to test the association of 19 EHR-derived phenotypes with 34 SNPs that were previously reported to be associated with BD. After Bonferroni multiple testing correction, P<7.7 × 10(-5) was considered statistically significant. The top association findings suggested that the BD risk alleles at SNP rs4765913 in CACNA1C gene and rs7042161 in SVEP1 may be associated with increased risk of 'cardiac dysrhythmias' (odds ratio (OR)=1.1, P=3.4 × 10(-3)) and 'essential hypertension' (OR=1.1, P=3.5 × 10(-3)), respectively. Although these associations are not statistically significant after multiple testing correction, both genes have been previously implicated with cardiovascular phenotypes. Moreover, we present additional evidence supporting these associations, particularly the association of the SVEP1 SNP with hypertension. This study shows the potential for EHR-based analyses of large cohorts to discover pleiotropic effects contributing to complex psychiatric traits and commonly co-occurring medical conditions.

Published
2016
Full Text
View/download PDF

7. Accumulating evidence for a role of TCF7L2 variants in bipolar disorder with elevated body mass index.

Author

Cuellar-Barboza AB, Winham SJ, McElroy SL, Geske JR, Jenkins GD, Colby CL, Prieto ML, Ryu E, Cunningham JM, Frye MA, and Biernacka JM

Subjects
Adult, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Bipolar Disorder diagnosis, Bipolar Disorder genetics, Body Mass Index, Transcription Factor 7-Like 2 Protein genetics
Abstract

Objectives: Bipolar disorder (BD) is a complex disease associated with various hereditary traits, including a higher body mass index (BMI). In a prior genome-wide association study, we found that BMI modified the association of rs12772424 - a common variant in the gene encoding transcription factor 7-like 2 (TCF7L2) - with risk for BD. TCF7L2 is a transcription factor in the canonical Wnt pathway, involved in multiple disorders, including diabetes, cancer and psychiatric conditions. Here, using an independent sample, we evaluated 26 TCF7L2 single nucleotide polymorphisms (SNPs) to explore further the association of BD with the TCF7L2-BMI interaction., Methods: Using a sample of 662 BD cases and 616 controls, we conducted SNP-level and gene-level tests to assess the evidence for an association between BD and the interaction of BMI and genetic variation in TCF7L2. We also explored the potential mechanism behind the detected associations using human brain expression quantitative trait loci (eQTL) analysis., Results: The analysis provided independent evidence of an rs12772424-BMI interaction (p = 0.011). Furthermore, while overall there was no evidence for SNP marginal effects on BD, the TCF7L2-BMI interaction was significant at the gene level (p = 0.042), with seven of the 26 SNPs showing SNP-BMI interaction effects with p < 0.05. The strongest evidence of interaction was observed for rs7895307 (p = 0.006). TCF7L2 expression showed a significant enrichment of association with the expression of other genes in the Wnt canonical pathway., Conclusions: The current study provides further evidence suggesting that TCF7L2 involvement in BD risk may be regulated by BMI. Detailed, prospective assessment of BMI, comorbidity, and other possible contributing factors is necessary to explain fully the mechanisms underlying this association., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2016
Full Text
View/download PDF

8. Association between history of psychosis and cardiovascular disease in bipolar disorder.

Author

Prieto ML, McElroy SL, Hayes SN, Sutor B, Kung S, Bobo WV, Fuentes ME, Cuellar-Barboza AB, Crow S, Ösby U, Chauhan M, Westman J, Geske JR, Colby CL, Ryu E, Biernacka JM, and Frye MA

Subjects
Adult, Age Factors, Aged, Bipolar Disorder classification, Bipolar Disorder psychology, Comorbidity, Cross-Sectional Studies, Diagnostic and Statistical Manual of Mental Disorders, Female, Humans, Hypertension epidemiology, Logistic Models, Male, Middle Aged, Odds Ratio, Psychotic Disorders psychology, Severity of Illness Index, Bipolar Disorder epidemiology, Cardiovascular Diseases epidemiology, Psychotic Disorders epidemiology
Abstract

Objectives: To determine whether clinical features of bipolar disorder, such as history of psychosis, and cardiovascular disease (CVD) risk factors contribute to a higher risk of CVD among patients with bipolar disorder., Methods: This cross-sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed by the Structured Clinical Interview for DSM-IV-TR disorders (SCID). Medical comorbidity burden was quantified utilizing the Cumulative Illness Severity Rating Scale (CIRS). This 13-item organ-based scale includes cardiac disease severity quantification. Confirmed by medical record review, patients who scored 1 (current mild or past significant problem) or higher in the cardiac item were compared by logistic regression to patients who scored 0 (no impairment), adjusting for CVD risk factors that were selected using a backwards stepwise approach or were obtained from the literature., Results: In a multivariate model, age [odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.66-5.54, p < 0.0001], hypertension (OR = 2.43, 95% CI: 1.69-3.55, p < 0.0001), and history of psychosis (OR = 1.48, 95% CI: 1.03-2.13, p = 0.03) were associated with CVD. When CVD risk factors from the literature were added to the analysis, age (OR = 3.19, 95% CI: 1.67-6.10, p = 0.0005) and hypertension (OR = 2.46, 95% CI: 1.61-3.76, p < 0.01) remained significant, with psychosis being at the trend level (OR = 1.43, 95% CI: 0.96-2.13, p = 0.08)., Conclusions: The phenotype of psychotic bipolar disorder may reflect higher illness severity with associated cardiac comorbidity. Further studies are encouraged to clarify the effect of the disease burden (i.e., depression), lifestyle, and treatment interventions (i.e., atypical antipsychotics) on this risk association., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2015
Full Text
View/download PDF

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

Author

Andlauer, Till F M, Guzman-Parra, Jose, Orozco Diaz, Guillermo, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, de Diego-Otero, Yolanda, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Parra, José Guzman, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Moreno-Küstner, Berta, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L, Auburger, Georg, Kittel-Schneider, Sarah, Knowles, James A, Kogevinas, Manolis, Koller, Anna C, Kupka, Ralph, Lavebratt, Catharina, Lawrence, Jacob, Lawson, William B, Leber, Markus, Lee, Phil H, Degenhardt, Franziska, Levy, Shawn E, Li, Jun Z, Liu, Chunyu, Lucae, Susanne, Maaser, Anna, MacIntyre, Donald J, Mahon, Pamela B, Maier, Wolfgang, Martinsson, Lina, McCarroll, Steve, Heilmann-Heimbach, Stefanie, McGuffin, Peter, McInnis, Melvin G, McKay, James D, Medeiros, Helena, Medland, Sarah E, Meng, Fan, Milani, Lili, Montgomery, Grant W, Morris, Derek W, Mühleisen, Thomas W, Mullins, Niamh, Nguyen, Hoang, Nievergelt, Caroline M, Adolfsson, Annelie Nordin, Nwulia, Evaristus A, O'Donovan, Claire, Loohuis, Loes M Olde, Ori, Anil P S, Oruc, Lilijana, Ösby, Urban, Perlis, Roy H, Perry, Amy, Pfennig, Andrea, Potash, James B, Purcell, Shaun M, Regeer, Eline J, Reif, Andreas, Reinbold, Céline S, Rice, John P, Richards, Alexander L, Frank, Josef, Rivas, Fabio, Rivera, Margarita, Roussos, Panos, Ruderfer, Douglas M, Ryu, Euijung, Sánchez-Mora, Cristina, Schatzberg, Alan F, Scheftner, William A, Schork, Nicholas J, Weickert, Cynthia Shannon, Foo, Jerome C, Shehktman, Tatyana, Shilling, Paul D, Sigurdsson, Engilbert, Slaney, Claire, Smeland, Olav B, Sobell, Janet L, Hansen, Christine Søholm, Spijker, Anne T, Clair, David St, Steffens, Michael, Streit, Fabian, Treutlein, Jens, Strauss, John S, Strohmaier, Jana, Szelinger, Szabolcs, Thompson, Robert C, EThorgeirsson, Thorgeir, Vedde, Helmut, Wang, Weiqing, Watson, Stanley J, Witt, Stephanie H, Weickert, Thomas W, Xi, Simon, Xu, Wei, Young, Allan H, Zandi, Peter, Zhang, Peng, Zollner, Sebastian, Adolfsson, Rolf, Agartz, Ingrid, Cichon, Sven, Alda, Martin, Backlund, Lena, Baune, Bernhard T, Bellivier, Frank, Berrettini, Wade H, Biernacka, Joanna M, Blackwood, Douglas H R, Boehnke, Michael, Børglum, Anders D, Corvin, Aiden, Craddock, Nicholas, Daly, Mark J, Dannlowski, Udo, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M, Gershon, Elliot S, Gill, Michael, Goes, Fernando, Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Hougaard, David M, Hultman, Christina M, Jones, Ian, Jones, Lisa A, Kahn, René S, Kirov, George, Landén, Mikael, Leboyer, Marion, Mayoral, Fermín, Lewis, Cathryn M, Li, Qingqin S, Lissowska, Jolanta, Martin, Nicholas G, Mayoral, Fermin, McElroy, Susan L, McIntosh, Andrew M, McMahon, Francis J, Melle, Ingrid, Metspalu, Andres, Müller-Myhsok, Bertram, Mitchell, Philip B, Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Myers, Richard M, Neale, Benjamin M, Nimgaonkar, Vishwajit, Nordentoft, Merete, Nöthen, Markus M, Forstner, Andreas J, O'Donovan, Michael C, Oedegaard, Ketil J, Owen, Michael J, Paciga, Sara A, Pato, Carlos, Pato, Michele T, Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Ribasés, Marta, Rietschel, Marcella, Rouleau, Guy A, Schalling, Martin, Schofield, Peter R, Schulze, Thomas G, Serretti, Alessandro, Smoller, Jordan W, Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Sullivan, Patrick F, Turecki, Gustavo, Vaaler, Arne E, Vieta, Eduard, Vincent, John B, Werge, Thomas, Nurnberger, John I, Wray, Naomi R, Florio, Arianna Di, Edenberg, Howard J, Stahl, Eli A, Ophoff, Roel A, Scott, Laura J, Andreassen, Ole A, Kelsoe, John, Sklar, Pamela, Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M, Breen, Gerome, Abdellaoui, Abdel, Adams, Mark J, Agerbo, Esben, Air, Tracy M, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T F, Bigdeli, Tim B, Binder, Elisabeth B, Bryois, Julien, Buttenschøn, Henriette N, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R I, Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, McQuillin, Andrew, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Deary, Ian J, Derks, Eske M, Direk, Nese, Dolan, Conor V, Dunn, Erin C, Eley, Thalia C, Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K, Gaspar, Héléna A, Goes, Fernando S, Trubetskoy, Vassily, Hall, Lynsey S, Hansen, Thomas F, Hickie, Ian B, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Howard, David M, Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Kohane, Isaac S, Kraft, Julia, Wang, Yunpeng, Kretzschmar, Warren W, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A, MacKinnon, Dean F, Maier, Robert M, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Mondimore, Francis M, Mostafavi, Sara, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, O'Reilly, Paul F, Oskarsson, Hogni, Painter, Jodie N, González, Maria José, de Leeuw, Christiaan A, Pedersen, Carsten Bøcker, Peterson, Roseann E, Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Quiroz, Jorge A, Qvist, Per, Steinberg, Stacy, Riley, Brien P, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Shi, Jianxin, Shyn, Stanley I, Sinnamon, Grant C B, Pavlides, Jennifer M Whitehead, Smit, Johannes H, Smith, Daniel J, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Thorgeirsson, Thorgeir E, Traylor, Matthew, Uitterlinden, André G, Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M, Viktorin, Alexander, Pers, Tune H, Visscher, Peter M, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Wu, Yang, Xi, Hualin S, Yang, Jian, Holmans, Peter A, Zhang, Futao, Arolt, Volker, Berger, Klaus, Boomsma, Dorret I, de Geus, E. J. C., DePaulo, J Raymond, Domenici, Enrico, Abbott, Liam, Domschke, Katharina, Grabe, Hans J, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Madden, Pamela A F, Magnusson, Patrik K, Akil, Huda, Pedersen, Nancy L, Penninx, Brenda W J H, Porteous, David J, Preisig, Martin, Albani, Diego, Schaefer, Catherine, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M, Gil Flores, Susana, Alliey-Rodriguez, Ney, Levinson, Douglas F, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Cabaleiro Fabeiro, Francisco J, Belliveau, Richard, Bergen, Sarah E, Bøen, Erlend, Boks, Marco, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Del Río Noriega, Francisco, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Coryell, William, Perez, Fermin Perez, Craig, David W, Cruceanu, Cristiana, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Del-Favero, Jurgen, Djurovic, Srdjan, Dobbyn, Amanda L, Haro González, Jesus, Dumont, Ashley, Elvsåshagen, Torbjørn, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Fraser, Christine, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Epidemiology and Data Science, APH - Digital Health, Andlauer T.F.M., Guzman-Parra J., Streit F., Strohmaier J., Gonzalez M.J., Gil Flores S., Cabaleiro Fabeiro F.J., del Rio Noriega F., Perez F.P., Haro Gonzalez J., Orozco Diaz G., de Diego-Otero Y., Moreno-Kustner B., Auburger G., Degenhardt F., Heilmann-Heimbach S., Herms S., Hoffmann P., Frank J., Foo J.C., Treutlein J., Witt S.H., Cichon S., Kogevinas M., Stahl E.A., Breen G., Forstner A.J., McQuillin A., Ripke S., Trubetskoy V., Mattheisen M., Wang Y., Coleman J.R.I., Gaspar H.A., de Leeuw C.A., Steinberg S., Pavlides J.M.W., Trzaskowski M., Pers T.H., Holmans P.A., Abbott L., Agerbo E., Akil H., Albani D., Alliey-Rodriguez N., Als T.D., Anjorin A., Antilla V., Awasthi S., Badner J.A., Baekvad-Hansen M., Barchas J.D., Bass N., Bauer M., Belliveau R., Bergen S.E., Pedersen C.B., Boen E., Boks M., Boocock J., Budde M., Bunney W., Burmeister M., Bybjerg-Grauholm J., Byerley W., Casas M., Cerrato F., Cervantes P., Chambert K., Charney A.W., Chen D., Churchhouse C., Clarke T.-K., Coryell W., Craig D.W., Cruceanu C., Czerski P.M., Dale A.M., de Jong S., Del-Favero J., DePaulo J.R., Djurovic S., Dobbyn A.L., Dumont A., Elvsashagen T., Escott-Price V., Fan C.C., Fischer S.B., Flickinger M., Foroud T.M., Forty L., Fraser C., Freimer N.B., Frisen L., Gade K., Gage D., Garnham J., Giambartolomei C., Pedersen M.G., Goldstein J., Gordon S.D., Gordon-Smith K., Green E.K., Green M.J., Greenwood T.A., Grove J., Guan W., Parra J.G., Hamshere M.L., Hautzinger M., Heilbronner U., Hipolito M., Holland D., Huckins L., Jamain S., Johnson J.S., Jureus A., Kandaswamy R., Karlsson R., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Koller A.C., Kupka R., Lavebratt C., Lawrence J., Lawson W.B., Leber M., Lee P.H., Levy S.E., Li J.Z., Liu C., Lucae S., Maaser A., MacIntyre D.J., Mahon P.B., Maier W., Martinsson L., McCarroll S., McGuffin P., McInnis M.G., McKay J.D., Medeiros H., Medland S.E., Meng F., Milani L., Montgomery G.W., Morris D.W., Muhleisen T.W., Mullins N., Nguyen H., Nievergelt C.M., Adolfsson A.N., Nwulia E.A., O'Donovan C., Loohuis L.M.O., Ori A.P.S., Oruc L., Osby U., Perlis R.H., Perry A., Pfennig A., Potash J.B., Purcell S.M., Regeer E.J., Reif A., Reinbold C.S., Rice J.P., Richards A.L., Rivas F., Rivera M., Roussos P., Ruderfer D.M., Ryu E., Sanchez-Mora C., Schatzberg A.F., Scheftner W.A., Schork N.J., Weickert C.S., Shehktman T., Shilling P.D., Sigurdsson E., Slaney C., Smeland O.B., Sobell J.L., Hansen C.S., Spijker A.T., Clair D.S., Steffens M., Strauss J.S., Szelinger S., Thompson R.C., EThorgeirsson T., Vedde H., Wang W., Watson S.J., Weickert T.W., Xi S., Xu W., Young A.H., Zandi P., Zhang P., Zollner S., Adolfsson R., Agartz I., Alda M., Backlund L., Baune B.T., Bellivier F., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boehnke M., Borglum A.D., Corvin A., Craddock N., Daly M.J., Dannlowski U., Esko T., Etain B., Frye M., Fullerton J.M., Gershon E.S., Gill M., Goes F., Grigoroiu-Serbanescu M., Hauser J., Hougaard D.M., Hultman C.M., Jones I., Jones L.A., Kahn R.S., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Martin N.G., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Metspalu A., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Muller-Myhsok B., Myers R.M., Neale B.M., Nimgaonkar V., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Owen M.J., Paciga S.A., Pato C., Pato M.T., Posthuma D., Ramos-Quiroga J.A., Ribases M., Rietschel M., Rouleau G.A., Schalling M., Schofield P.R., Schulze T.G., Serretti A., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Werge T., Nurnberger J.I., Wray N.R., Florio A.D., Edenberg H.J., Ophoff R.A., Scott L.J., Andreassen O.A., Kelsoe J., Sklar P., Byrne E.M., Abdellaoui A., Adams M.J., Air T.M., Bacanu S.-A., Beekman A.T.F., Bigdeli T.B., Binder E.B., Bryois J., Buttenschon H.N., Cai N., Castelao E., Christensen J.H., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Deary I.J., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Kiadeh F.F.H., Finucane H.K., Goes F.S., Hall L.S., Hansen T.F., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Howard D.M., Ising M., Jansen R., Jorgenson E., Kohane I.S., Hill, Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacKinnon D.F., Maier R.M., Marchini J., Mbarek H., McGrath P., Mehta D., Middeldorp C.M., Mihailov E., Milaneschi Y., Mondimore F.M., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Painter J.N., Peterson R.E., Pettersson E., Peyrot W.J., Pistis G., Quiroz J.A., Qvist P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Shi J., Shyn S.I., Sinnamon G.C.B., Smit J.H., Smith D.J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Uitterlinden A.G., Umbricht D., Van der Auwera S., van Hemert A.M., Viktorin A., Visscher P.M., Webb B.T., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Berger K., Boomsma D.I., de Geus E.J.C., Domenici E., Domschke K., Grabe H.J., Hamilton S.P., Hayward C., Heath A.C., Kendler K.S., Kloiber S., Lewis G., Madden P.A.F., Magnusson P.K., Pedersen N.L., Penninx B.W.J.H., Porteous D.J., Preisig M., Schaefer C., Tiemeier H., Uher R., Volzke H., Weissman M.M., Levinson D.F., Child and Adolescent Psychiatry / Psychology, Epidemiology, Internal Medicine, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, and Adult Psychiatry

Subjects
Netherlands Twin Register (NTR), Genetic variants, Bipolar Disorder, Specific risk, Disease, 0302 clinical medicine, Multiplex, Genetic risk, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Depression (differential diagnoses), 0303 health sciences, Depression, ddc, 3. Good health, Geðraskanir, Psychiatry and Mental health, Schizophrenia, Cohort, Major depressive disorder, Case-Control Studie, Human, medicine.medical_specialty, Bipolar disorder, Article, Cellular and Molecular Neuroscience, 03 medical and health sciences, Geðklofi, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Psychiatry, Þunglyndi, Molecular Biology, 030304 developmental biology, Depressive Disorder, Major, Geðhvarfasýki, business.industry, Psychiatric disorder, medicine.disease, Genarannsóknir, Case-Control Studies, Multiple comparisons problem, business, 030217 neurology & neurosurgery
Abstract

Publisher's version, 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., The study was supported by the German Federal Ministry of Education and Research (BMBF), through the Integrated Network IntegraMent, under the auspices of the e:Med programme (grants 01ZX1314A to MMN and SC; 01ZX1314G to MR; 01ZX1614J to BMM) through grants 01EE1406C to MR and 01EE1409C to MR and SHW, and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” (01EW1810 to MR) and BMBF grants 01EE1409C and 01EE1406C to MR and SHW; by the German Research Foundation (DFG grants FOR2107; RI908/11-2 to MR; NO246/10-2 to MMN; MU1315/8-2 to BMM; WI 3439/3-2 to SHW), by the Andalusian regional Health and Innovation Government (grants PI-0060-2017, RC-0006-2015 the Nicolas Monarde Programme for YDO and CTS-546) and by the Swiss National Science Foundation (SNSF grant 156791 to SC). MMN is a member of the DFG-funded cluster of excellence ImmunoSensation. The PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320). We thank the research participants and employees of 23andMe, Inc. for their contribution to the MDD meta-analysis published in [14]. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for the present analyses. See the Supplementary Data for extended Acknowledgements.

Published
2021
Full Text
View/download PDF

10. The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

Author

Jonathan R.I. Coleman, Héléna A. Gaspar, Julien Bryois, Gerome Breen, Enda M. Byrne, Andreas J. Forstner, Peter A. Holmans, Christiaan A. de Leeuw, Manuel Mattheisen, Andrew McQuillin, Jennifer M. Whitehead Pavlides, Tune H. Pers, Stephan Ripke, Eli A. Stahl, Stacy Steinberg, Vassily Trubetskoy, Maciej Trzaskowski, Yunpeng Wang, Liam Abbott, Abdel Abdellaoui, Mark J. Adams, Annelie Nordin Adolfsson, Esben Agerbo, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Thomas D. Als, Till F.M. Andlauer, Adebayo Anjorin, Verneri Antilla, Sandra Van der Auwera, Swapnil Awasthi, Silviu-Alin Bacanu, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Aartjan T.F. Beekman, Richard Belliveau, Sarah E. Bergen, Tim B. Bigdeli, Elisabeth B. Binder, Erlend Bøen, Marco Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, William Byerley, Na Cai, Miquel Casas, Enrique Castelao, Felecia Cerrato, Pablo Cervantes, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Jane Hvarregaard Christensen, Claire Churchhouse, David St Clair, Toni-Kim Clarke, Lucía Colodro-Conde, William Coryell, Baptiste Couvy-Duchesne, David W. Craig, Gregory E. Crawford, Cristiana Cruceanu, Piotr M. Czerski, Anders M. Dale, Gail Davies, Ian J. Deary, Franziska Degenhardt, Jurgen Del-Favero, J Raymond DePaulo, Eske M. Derks, Nese Direk, Srdjan Djurovic, Amanda L. Dobbyn, Conor V. Dolan, Ashley Dumont, Erin C. Dunn, Thalia C. Eley, Torbjørn Elvsåshagen, Valentina Escott-Price, Chun Chieh Fan, Hilary K. Finucane, Sascha B. Fischer, Matthew Flickinger, Jerome C. Foo, Tatiana M. Foroud, Liz Forty, Josef Frank, Christine Fraser, Nelson B. Freimer, Louise Frisén, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Fernando S. Goes, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Melissa J. Green, Tiffany A. Greenwood, Jakob Grove, Weihua Guan, Lynsey S. Hall, Marian L. Hamshere, Christine Søholm Hansen, Thomas F. Hansen, Martin Hautzinger, Urs Heilbronner, Albert M. van Hemert, Stefan Herms, Ian B. Hickie, Maria Hipolito, Per Hoffmann, Dominic Holland, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, Laura Huckins, Marcus Ising, Stéphane Jamain, Rick Jansen, Jessica S. Johnson, Simone de Jong, Eric Jorgenson, Anders Juréus, Radhika Kandaswamy, Robert Karlsson, James L. Kennedy, Farnush Farhadi Hassan Kiadeh, Sarah Kittel-Schneider, James A. Knowles, Manolis Kogevinas, Isaac S. Kohane, Anna C. Koller, Julia Kraft, Warren W. Kretzschmar, Jesper Krogh, Ralph Kupka, Zoltán Kutalik, Catharina Lavebratt, Jacob Lawrence, William B. Lawson, Markus Leber, Phil H. Lee, Shawn E. Levy, Jun Z. Li, Yihan Li, Penelope A. Lind, Chunyu Liu, Loes M. Olde Loohuis, Anna Maaser, Donald J. MacIntyre, Dean F. MacKinnon, Pamela B. Mahon, Wolfgang Maier, Robert M. Maier, Jonathan Marchini, Lina Martinsson, Hamdi Mbarek, Steve McCarroll, Patrick McGrath, Peter McGuffin, Melvin G. McInnis, James D. McKay, Helena Medeiros, Sarah E. Medland, Divya Mehta, Fan Meng, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Saira Saeed Mirza, Francis M. Mondimore, Grant W. Montgomery, Derek W. Morris, Sara Mostafavi, Thomas W. Mühleisen, Niamh Mullins, Matthias Nauck, Bernard Ng, Hoang Nguyen, Caroline M. Nievergelt, Michel G. Nivard, Evaristus A. Nwulia, Dale R. Nyholt, Claire O'Donovan, Paul F. O'Reilly, Anil P.S. Ori, Lilijana Oruc, Urban Ösby, Hogni Oskarsson, Jodie N. Painter, José Guzman Parra, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Amy Perry, Roseann E. Peterson, Erik Pettersson, Wouter J. Peyrot, Andrea Pfennig, Giorgio Pistis, Shaun M. Purcell, Jorge A. Quiroz, Per Qvist, Eline J. Regeer, Andreas Reif, Céline S. Reinbold, John P. Rice, Brien P. Riley, Fabio Rivas, Margarita Rivera, Panos Roussos, Douglas M. Ruderfer, Euijung Ryu, Cristina Sánchez-Mora, Alan F. Schatzberg, William A. Scheftner, Robert Schoevers, Nicholas J. Schork, Eva C. Schulte, Tatyana Shehktman, Ling Shen, Jianxin Shi, Paul D. Shilling, Stanley I. Shyn, Engilbert Sigurdsson, Claire Slaney, Olav B. Smeland, Johannes H. Smit, Daniel J. Smith, Janet L. Sobell, Anne T. Spijker, Michael Steffens, John S. Strauss, Fabian Streit, Jana Strohmaier, Szabolcs Szelinger, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Robert C. Thompson, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, André G. Uitterlinden, Daniel Umbricht, Helmut Vedder, Alexander Viktorin, Peter M. Visscher, Weiqing Wang, Stanley J. Watson, Bradley T. Webb, Cynthia Shannon Weickert, Thomas W. Weickert, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Wei Xu, Jian Yang, Allan H. Young, Peter Zandi, Peng Zhang, Futao Zhang, Sebastian Zollner, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Volker Arolt, Lena Backlund, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Wade H. Berrettini, Joanna M. Biernacka, Douglas H.R. Blackwood, Michael Boehnke, Dorret I. Boomsma, Aiden Corvin, Nicholas Craddock, Mark J. Daly, Udo Dannlowski, Enrico Domenici, Katharina Domschke, Tõnu Esko, Bruno Etain, Mark Frye, Janice M. Fullerton, Elliot S. Gershon, E.J.C. de Geus, Michael Gill, Fernando Goes, Hans J. Grabe, Maria Grigoroiu-Serbanescu, Steven P. Hamilton, Joanna Hauser, Caroline Hayward, Andrew C. Heath, David M. Hougaard, Christina M. Hultman, Ian Jones, Lisa A. Jones, René S. Kahn, Kenneth S. Kendler, George Kirov, Stefan Kloiber, Mikael Landén, Marion Leboyer, Glyn Lewis, Qingqin S. Li, Jolanta Lissowska, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Nicholas G. Martin, Fermin Mayoral, Susan L. McElroy, Andrew M. McIntosh, Francis J. McMahon, Ingrid Melle, Andres Metspalu, Philip B. Mitchell, Gunnar Morken, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Richard M. Myers, Benjamin M. Neale, Vishwajit Nimgaonkar, Merete Nordentoft, Markus M. Nöthen, Michael C. O'Donovan, Ketil J. Oedegaard, Michael J. Owen, Sara A. Paciga, Carlos Pato, Michele T. Pato, Nancy L. Pedersen, Brenda W.J. H. Penninx, Roy H. Perlis, David J. Porteous, Danielle Posthuma, James B. Potash, Martin Preisig, Josep Antoni Ramos-Quiroga, Marta Ribasés, Marcella Rietschel, Guy A. Rouleau, Catherine Schaefer, Martin Schalling, Peter R. Schofield, Thomas G. Schulze, Alessandro Serretti, Jordan W. Smoller, Hreinn Stefansson, Kari Stefansson, Eystein Stordal, Henning Tiemeier, Gustavo Turecki, Rudolf Uher, Arne E. Vaaler, Eduard Vieta, John B. Vincent, Henry Völzke, Myrna M. Weissman, Thomas Werge, Ole A. Andreassen, Anders D. Børglum, Sven Cichon, Howard J. Edenberg, Arianna Di Florio, John Kelsoe, Douglas F. Levinson, Cathryn M. Lewis, John I. Nurnberger, Roel A. Ophoff, Laura J. Scott, Pamela Sklar, Patrick F. Sullivan, Naomi R. Wray, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Epidemiology, Erasmus MC other, Urology, Psychiatry, Internal Medicine, Medical Informatics, Immunology, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, Coleman J.R.I., Gaspar H.A., Bryois J., Byrne E.M., Forstner A.J., Holmans P.A., de Leeuw C.A., Mattheisen M., McQuillin A., Whitehead Pavlides J.M., Pers T.H., Ripke S., Stahl E.A., Steinberg S., Trubetskoy V., Trzaskowski M., Wang Y., Abbott L., Abdellaoui A., Adams M.J., Adolfsson A.N., Agerbo E., Akil H., Albani D., Alliey-Rodriguez N., Als T.D., Andlauer T.F.M., Anjorin A., Antilla V., Van der Auwera S., Awasthi S., Bacanu S.-A., Badner J.A., Baekvad-Hansen M., Barchas J.D., Bass N., Bauer M., Beekman A.T.F., Belliveau R., Bergen S.E., Bigdeli T.B., Binder E.B., Boen E., Boks M., Boocock J., Budde M., Bunney W., Burmeister M., Buttenschon H.N., Bybjerg-Grauholm J., Byerley W., Cai N., Casas M., Castelao E., Cerrato F., Cervantes P., Chambert K., Charney A.W., Chen D., Christensen J.H., Churchhouse C., St Clair D., Clarke T.-K., Colodro-Conde L., Coryell W., Couvy-Duchesne B., Craig D.W., Crawford G.E., Cruceanu C., Czerski P.M., Dale A.M., Davies G., Deary I.J., Degenhardt F., Del-Favero J., DePaulo J.R., Derks E.M., Direk N., Djurovic S., Dobbyn A.L., Dolan C.V., Dumont A., Dunn E.C., Eley T.C., Elvsashagen T., Escott-Price V., Fan C.C., Finucane H.K., Fischer S.B., Flickinger M., Foo J.C., Foroud T.M., Forty L., Frank J., Fraser C., Freimer N.B., Frisen L., Gade K., Gage D., Garnham J., Giambartolomei C., Goes F.S., Goldstein J., Gordon S.D., Gordon-Smith K., Green E.K., Green M.J., Greenwood T.A., Grove J., Guan W., Hall L.S., Hamshere M.L., Hansen C.S., Hansen T.F., Hautzinger M., Heilbronner U., van Hemert A.M., Herms S., Hickie I.B., Hipolito M., Hoffmann P., Holland D., Homuth G., Horn C., Hottenga J.-J., Huckins L., Ising M., Jamain S., Jansen R., Johnson J.S., de Jong S., Jorgenson E., Jureus A., Kandaswamy R., Karlsson R., Kennedy J.L., Hassan Kiadeh F.F., Kittel-Schneider S., Knowles J.A., Kogevinas M., Kohane I.S., Koller A.C., Kraft J., Kretzschmar W.W., Krogh J., Kupka R., Kutalik Z., Lavebratt C., Lawrence J., Lawson W.B., Leber M., Lee P.H., Levy S.E., Li J.Z., Li Y., Lind P.A., Liu C., Olde Loohuis L.M., Maaser A., MacIntyre D.J., MacKinnon D.F., Mahon P.B., Maier W., Maier R.M., Marchini J., Martinsson L., Mbarek H., McCarroll S., McGrath P., McGuffin P., McInnis M.G., McKay J.D., Medeiros H., Medland S.E., Mehta D., Meng F., Middeldorp C.M., Mihailov E., Milaneschi Y., Milani L., Mirza S.S., Mondimore F.M., Montgomery G.W., Morris D.W., Mostafavi S., Muhleisen T.W., Mullins N., Nauck M., Ng B., Nguyen H., Nievergelt C.M., Nivard M.G., Nwulia E.A., Nyholt D.R., O'Donovan C., O'Reilly P.F., Ori A.P.S., Oruc L., Osby U., Oskarsson H., Painter J.N., Parra J.G., Pedersen C.B., Pedersen M.G., Perry A., Peterson R.E., Pettersson E., Peyrot W.J., Pfennig A., Pistis G., Purcell S.M., Quiroz J.A., Qvist P., Regeer E.J., Reif A., Reinbold C.S., Rice J.P., Riley B.P., Rivas F., Rivera M., Roussos P., Ruderfer D.M., Ryu E., Sanchez-Mora C., Schatzberg A.F., Scheftner W.A., Schoevers R., Schork N.J., Schulte E.C., Shehktman T., Shen L., Shi J., Shilling P.D., Shyn S.I., Sigurdsson E., Slaney C., Smeland O.B., Smit J.H., Smith D.J., Sobell J.L., Spijker A.T., Steffens M., Strauss J.S., Streit F., Strohmaier J., Szelinger S., Tansey K.E., Teismann H., Teumer A., Thompson R.C., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Uitterlinden A.G., Umbricht D., Vedder H., Viktorin A., Visscher P.M., Wang W., Watson S.J., Webb B.T., Weickert C.S., Weickert T.W., Weinsheimer S.M., Wellmann J., Willemsen G., Witt S.H., Wu Y., Xi H.S., Xu W., Yang J., Young A.H., Zandi P., Zhang P., Zhang F., Zollner S., Adolfsson R., Agartz I., Alda M., Arolt V., Backlund L., Baune B.T., Bellivier F., Berger K., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boehnke M., Boomsma D.I., Corvin A., Craddock N., Daly M.J., Dannlowski U., Domenici E., Domschke K., Esko T., Etain B., Frye M., Fullerton J.M., Gershon E.S., de Geus E.J.C., Gill M., Goes F., Grabe H.J., Grigoroiu-Serbanescu M., Hamilton S.P., Hauser J., Hayward C., Heath A.C., Hougaard D.M., Hultman C.M., Jones I., Jones L.A., Kahn R.S., Kendler K.S., Kirov G., Kloiber S., Landen M., Leboyer M., Lewis G., Li Q.S., Lissowska J., Lucae S., Madden P.A.F., Magnusson P.K., Martin N.G., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Metspalu A., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Muller-Myhsok B., Myers R.M., Neale B.M., Nimgaonkar V., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Owen M.J., Paciga S.A., Pato C., Pato M.T., Pedersen N.L., Penninx B.W.J.H., Perlis R.H., Porteous D.J., Posthuma D., Potash J.B., Preisig M., Ramos-Quiroga J.A., Ribases M., Rietschel M., Rouleau G.A., Schaefer C., Schalling M., Schofield P.R., Schulze T.G., Serretti A., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Tiemeier H., Turecki G., Uher R., Vaaler A.E., Vieta E., Vincent J.B., Volzke H., Weissman M.M., Werge T., Andreassen O.A., Borglum A.D., Cichon S., Edenberg H.J., Di Florio A., Kelsoe J., Levinson D.F., Lewis C.M., Nurnberger J.I., Ophoff R.A., Scott L.J., Sklar P., Sullivan P.F., Wray N.R., and Breen G.

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Genetic correlation, Genome-wide association study, Mood Disorder, Bipolar disorder, Population, BF, Genomics, Major depressive disorder, Affective disorder, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, mental disorders, medicine, Animals, ddc:610, education, Depression (differential diagnoses), Biological Psychiatry, 030304 developmental biology, Genetic association, Genetics, Depressive Disorder, Major, 0303 health sciences, education.field_of_study, Animal, business.industry, Risk Factor, medicine.disease, 3. Good health, Affective disorders, 030104 developmental biology, Mood, Mood disorders, RC0321, Biological psychiatry, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

BackgroundMood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders.MethodsTo clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424).ResultsSeventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder.ConclusionsThe mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

Published
2020
Full Text
View/download PDF

11. Genome-wide association study identifies 30 loci associated with bipolar disorder

Author

Euijung Ryu, Danfeng Chen, Allan H. Young, Olav B. Smeland, James McKay, Frank Bellivier, Qingqin S. Li, Yunpeng Wang, Tõnu Esko, Bertram Müller-Myhsok, Weiqing Wang, Thomas W. Weickert, Joanna M. Biernacka, Ralph W. Kupka, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Marian L. Hamshere, Derek W. Morris, Douglas M. Ruderfer, Stephan Ripke, Nelson B. Freimer, Tatiana Foroud, Shaun Purcell, Ashley Dumont, Shawn Levy, Dominic Holland, Joanna Hauser, Anders D. Børglum, Liz Forty, Alan F. Schatzberg, Christine Fraser, Jennifer M. Whitehead Pavlides, William E. Bunney, Merete Nordentoft, Andres Metspalu, Gunnar Morken, Susanne Lucae, Roy H. Perlis, Anne T. Spijker, Richard A. Belliveau, Sarah E. Bergen, Fan Meng, Eduard Vieta, Cynthia Shannon Weickert, J. Raymond DePaulo, Martin Alda, Lina Martinsson, Melvin G. McInnis, Jacob Lawrence, Markus Leber, James A. Knowles, Franziska Degenhardt, Melissa J. Green, Jaqueline Goldstein, Amanda Dobbyn, Radhika Kandaswamy, Steve McCarroll, Katrin Gade, Jack D. Barchas, Christina M. Hultman, Sarah Kittel-Schneider, Martin Hautzinger, Maria Hipolito, Louise Frisén, Kari Stefansson, Michael Conlon O'Donovan, Markus M. Nöthen, Eline J. Regeer, Jens Treutlein, Robert Karlsson, Ian Jones, Nicholas G. Martin, William A. Scheftner, Caroline M. Nievergelt, Marta Ribasés, Simone de Jong, Szabolcs Szelinger, Thomas W. Mühleisen, Michele T. Pato, Manuel Mattheisen, Maciej Trzaskowski, Urs Heilbronner, Diane Gage, Jakob Grove, Ingrid Melle, Ole A. Andreassen, Claudia Giambartolomei, Kimberly Chambert, Arne E. Vaaler, William Coryell, Peter R. Schofield, Preben Bo Mortensen, Roel A. Ophoff, Fabian Streit, Manolis Kogevinas, Ingrid Agartz, John Strauss, James L. Kennedy, Anders M. Dale, Stefan Herms, Douglas Blackwood, Torbjørn Elvsåshagen, Bernhard T. Baune, Grant W. Montgomery, Andreas Reif, Fabio Rivas, Andrew McQuillin, Jordan W. Smoller, Chun Chieh Fan, James B. Potash, Jun Li, Ketil J. Oedegaard, David Curtis, Martin Schalling, John R. Kelsoe, Valentina Escott-Price, Sascha B. Fischer, Tatyana Shehktman, Jonathan R. I. Coleman, Stanley J. Watson, Donald J. MacIntyre, Tune H. Pers, Eystein Stordal, Richard M. Myers, Jose Guzman-Parra, Danielle Posthuma, John I. Nurnberger, William Lawson, Janet L. Sobell, Felecia Cerrato, Judith A. Badner, Elliot S. Gershon, Gerome Breen, Naomi R. Wray, Thomas Werge, Lilijana Oruc, Claire Slaney, Anil P.S. Ori, Alexander W. Charney, Marianne Giørtz Pedersen, Marie Bækvad-Hansen, Michael Boehnke, Marcella Rietschel, George Kirov, Aiden Corvin, Piotr M. Czerski, Peter Holmans, Michael Steffens, Margarita Rivera, Maria Grigoroiu-Serbanescu, René S. Kahn, Laura M. Huckins, Monika Budde, Michael Gill, Lili Milani, Christiaan de Leeuw, Peng Zhang, Nicholas Bass, Jana Strohmaier, John P. Rice, Wei Xu, Cristiana Cruceanu, Vassily Trubetskoy, Philip B. Mitchell, Helena Medeiros, Thomas Damm Als, Anna C. Koller, Huda Akil, Jessica S. Johnson, Toni-Kim Clarke, Janice M. Fullerton, Guy A. Rouleau, Fernando S. Goes, Weihua Guan, Wolfgang Maier, Pamela Sklar, Diego Albani, Laura J. Scott, Pamela B. Mahon, Anna Maaser, Katherine Gordon-Smith, Urban Ösby, Jurgen Del-Favero, Jolanta Lissowska, Howard J. Edenberg, Sven Cichon, Annelie Nordin Adolfsson, Julie Garnham, Josef Frank, Hoang T. Nguyen, Michael Bauer, Helmut Vedder, Vishwajit L. Nimgaonkar, Loes M. Olde Loohuis, Thomas G. Schulze, Cristina Sánchez-Mora, Udo Dannlowski, Rolf Adolfsson, Benjamin M. Neale, Verneri Antilla, Andrea Pfennig, John B. Vincent, Niamh Mullins, Per Hoffmann, Peter McGuffin, Erlend Bøen, Ney Alliey-Rodriguez, Adebayo Anjorin, Fermín Mayoral, Arianna Di Florio, Claire Churchhouse, David M. Hougaard, Nicholas J. Schork, Tiffany A. Greenwood, Carlos N. Pato, Thorgeir E. Thorgeirsson, Nicholas John Craddock, Stephanie H. Witt, Liam Abbott, Swapnil Awasthi, Miquel Casas, Jonas Bybjerg-Grauholm, Cathryn M. Lewis, Srdjan Djurovic, Bruno Etain, Margit Burmeister, Phil Lee, Elaine K. Green, Sara A. Paciga, Lena Backlund, Engilbert Sigurdsson, Patrick F. Sullivan, Amy Perry, Pablo Cervantes, Marco P. Boks, Catharina Lavebratt, Andrew M. McIntosh, Panos Roussos, Enda M. Byrne, Alexander Richards, Eli A. Stahl, Stéphane Jamain, Hreinn Stefansson, Ole Mors, Esben Agerbo, Susan L. McElroy, Wade H. Berrettini, Peter P. Zandi, Lisa Jones, Andreas J. Forstner, Alessandro Serretti, Céline S. Reinbold, Robert C. Thompson, Matthew Flickinger, William Byerley, Michael John Owen, Helena Gaspar, Francis J. McMahon, David St Clair, Mark A. Frye, Christine Søholm Hansen, Scott D. Gordon, Mikael Landén, Gustavo Turecki, Simon Xi, Evaristus A. Nwulia, Anders Juréus, James Boocock, Stacy Steinberg, Paul D. Shilling, David Craig, Mark J. Daly, Sarah E. Medland, Marion Leboyer, Chunyu Liu, Carsten Bøcker Pedersen, Sebastian Zöllner, APH - Mental Health, Psychiatry, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Stahl E.A., Breen G., Forstner A.J., McQuillin A., Ripke S., Trubetskoy V., Mattheisen M., Wang Y., Coleman J.R.I., Gaspar H.A., de Leeuw C.A., Steinberg S., Pavlides J.M.W., Trzaskowski M., Byrne E.M., Pers T.H., Holmans P.A., Richards A.L., Abbott L., Agerbo E., Akil H., Albani D., Alliey-Rodriguez N., Als T.D., Anjorin A., Antilla V., Awasthi S., Badner J.A., Baekvad-Hansen M., Barchas J.D., Bass N., Bauer M., Belliveau R., Bergen S.E., Pedersen C.B., Boen E., Boks M.P., Boocock J., Budde M., Bunney W., Burmeister M., Bybjerg-Grauholm J., Byerley W., Casas M., Cerrato F., Cervantes P., Chambert K., Charney A.W., Chen D., Churchhouse C., Clarke T.-K., Coryell W., Craig D.W., Cruceanu C., Curtis D., Czerski P.M., Dale A.M., de Jong S., Degenhardt F., Del-Favero J., DePaulo J.R., Djurovic S., Dobbyn A.L., Dumont A., Elvsashagen T., Escott-Price V., Fan C.C., Fischer S.B., Flickinger M., Foroud T.M., Forty L., Frank J., Fraser C., Freimer N.B., Frisen L., Gade K., Gage D., Garnham J., Giambartolomei C., Pedersen M.G., Goldstein J., Gordon S.D., Gordon-Smith K., Green E.K., Green M.J., Greenwood T.A., Grove J., Guan W., Guzman-Parra J., Hamshere M.L., Hautzinger M., Heilbronner U., Herms S., Hipolito M., Hoffmann P., Holland D., Huckins L., Jamain S., Johnson J.S., Jureus A., Kandaswamy R., Karlsson R., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koller A.C., Kupka R., Lavebratt C., Lawrence J., Lawson W.B., Leber M., Lee P.H., Levy S.E., Li J.Z., Liu C., Lucae S., Maaser A., MacIntyre D.J., Mahon P.B., Maier W., Martinsson L., McCarroll S., McGuffin P., McInnis M.G., McKay J.D., Medeiros H., Medland S.E., Meng F., Milani L., Montgomery G.W., Morris D.W., Muhleisen T.W., Mullins N., Nguyen H., Nievergelt C.M., Adolfsson A.N., Nwulia E.A., O'Donovan C., Loohuis L.M.O., Ori A.P.S., Oruc L., Osby U., Perlis R.H., Perry A., Pfennig A., Potash J.B., Purcell S.M., Regeer E.J., Reif A., Reinbold C.S., Rice J.P., Rivas F., Rivera M., Roussos P., Ruderfer D.M., Ryu E., Sanchez-Mora C., Schatzberg A.F., Scheftner W.A., Schork N.J., Shannon Weickert C., Shehktman T., Shilling P.D., Sigurdsson E., Slaney C., Smeland O.B., Sobell J.L., Soholm Hansen C., Spijker A.T., St Clair D., Steffens M., Strauss J.S., Streit F., Strohmaier J., Szelinger S., Thompson R.C., Thorgeirsson T.E., Treutlein J., Vedder H., Wang W., Watson S.J., Weickert T.W., Witt S.H., Xi S., Xu W., Young A.H., Zandi P., Zhang P., Zollner S., Adolfsson R., Agartz I., Alda M., Backlund L., Baune B.T., Bellivier F., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boehnke M., Borglum A.D., Corvin A., Craddock N., Daly M.J., Dannlowski U., Esko T., Etain B., Frye M., Fullerton J.M., Gershon E.S., Gill M., Goes F., Grigoroiu-Serbanescu M., Hauser J., Hougaard D.M., Hultman C.M., Jones I., Jones L.A., Kahn R.S., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Martin N.G., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Metspalu A., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Muller-Myhsok B., Myers R.M., Neale B.M., Nimgaonkar V., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Owen M.J., Paciga S.A., Pato C., Pato M.T., Posthuma D., Ramos-Quiroga J.A., Ribases M., Rietschel M., Rouleau G.A., Schalling M., Schofield P.R., Schulze T.G., Serretti A., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Werge T., Nurnberger J.I., Wray N.R., Di Florio A., Edenberg H.J., Cichon S., Ophoff R.A., Scott L.J., Andreassen O.A., Kelsoe J., Sklar P., eQTLGen Consortium, BIOS Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, and Complex Trait Genetics

Subjects
Male, Bipolar Disorder, Bipolar I disorder, Schizophrenia/genetics, LD SCORE REGRESSION, Genome-wide association study, VARIANTS, Bipolar II disorder, 0302 clinical medicine, SCHIZOPHRENIA, GWAS, Psychotic Disorders/genetics, Non-U.S. Gov't, RISK, Genetics, 0303 health sciences, HERITABILITY, Research Support, Non-U.S. Gov't, Systems Biology, Major/genetics, Single Nucleotide, 3. Good health, Schizophrenia, Major depressive disorder, Female, Case-Control Studie, Depressive Disorder, Major/genetics, Human, Psychosis, GENES, Biology, Psychotic Disorder, Research Support, Polymorphism, Single Nucleotide, Article, Bipolar Disorder/classification, N.I.H, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Journal Article, POLYGENICITY, Humans, Genetic Predisposition to Disease, Bipolar disorder, Polymorphism, METAANALYSIS, 030304 developmental biology, Intramural, Depressive Disorder, Major, Depressive Disorder, Genetic heterogeneity, Research Support, N.I.H., Intramural, medicine.disease, INDIVIDUALS, Psychotic Disorders, Genetic Loci, Case-Control Studies, Human medicine, 030217 neurology & neurosurgery, Genome-Wide Association Study, Meta-Analysis
Abstract

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu)., Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P, This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch.

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results