The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls.
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Keyword
Affective disordersBipolar disorder
Genetic correlation
Genome-wide association study
Major depressive disorder
Mood disorders
Journal title
Biological psychiatryDate Published
2019-11-01Publication Volume
88Publication Issue
2Publication Begin page
169Publication End page
184
Metadata
Show full item recordAbstract
Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction.To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium 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; nonoverlapping N = 609,424).
Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for 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-the relationship is positive in bipolar disorder but negative in major depressive disorder.
The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.
Citation
Coleman JRI, Gaspar HA, Bryois J; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Breen G. The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biol Psychiatry. 2020 Jul 15;88(2):169-184. doi: 10.1016/j.biopsych.2019.10.015. Epub 2019 Nov 1. PMID: 31926635; PMCID: PMC8136147.DOI
10.1016/j.biopsych.2019.10.015ae974a485f413a2113503eed53cd6c53
10.1016/j.biopsych.2019.10.015
Scopus Count
Collections
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Related articles
- GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.
- Authors: Mullins N, Bigdeli TB, Børglum AD, Coleman JRI, Demontis D, Mehta D, Power RA, Ripke S, Stahl EA, Starnawska A, Anjorin A, M.R.C.Psych, Corvin A, Sanders AR, Forstner AJ, Reif A, Koller AC, Świątkowska B, Baune BT, Müller-Myhsok B, Penninx BWJH, Pato C, Zai C, Rujescu D, Hougaard DM, Quested D, Levinson DF, Binder EB, Byrne EM, Agerbo E, Dr.Med.Sc, Streit F, Mayoral F, Bellivier F, Degenhardt F, Breen G, Morken G, Turecki G, Rouleau GA, Grabe HJ, Völzke H, Jones I, Giegling I, Agartz I, Melle I, Lawrence J, M.R.C.Psych, Walters JTR, Strohmaier J, Shi J, Hauser J, Biernacka JM, Vincent JB, Kelsoe J, Strauss JS, Lissowska J, Pimm J, M.R.C.Psych, Smoller JW, Guzman-Parra J, Berger K, Scott LJ, Jones LA, Azevedo MH, Trzaskowski M, Kogevinas M, Rietschel M, Boks M, Ising M, Grigoroiu-Serbanescu M, Hamshere ML, Leboyer M, Frye M, Nöthen MM, Alda M, Preisig M, Nordentoft M, Boehnke M, O'Donovan MC, Owen MJ, Pato MT, Renteria ME, Budde M, Dipl.-Psych, Weissman MM, Wray NR, Bass N, M.R.C.Psych, Craddock N, Smeland OB, Andreassen OA, Mors O, Gejman PV, Sklar P, McGrath P, Hoffmann P, McGuffin P, Lee PH, Mortensen PB, Kahn RS, Ophoff RA, Adolfsson R, Van der Auwera S, Djurovic S, Kloiber S, Heilmann-Heimbach S, Jamain S, Hamilton SP, McElroy SL, Lucae S, Cichon S, Schulze TG, Hansen T, Werge T, Air TM, Nimgaonkar V, Appadurai V, Cahn W, Milaneschi Y, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Fanous AH, Kendler KS, McQuillin A, Lewis CM
- Issue date: 2019 Aug 1
- Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders.
- Authors: 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, Advanced Collaborative Study of Mood Disorder (COSMO) Team, MooDS Bipolar Consortium
- Issue date: 2017 Dec 11
- Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
- Authors: Power RA, Tansey KE, Buttenschøn HN, Cohen-Woods S, Bigdeli T, Hall LS, Kutalik Z, Lee SH, Ripke S, Steinberg S, Teumer A, Viktorin A, Wray NR, Arolt V, Baune BT, Boomsma DI, Børglum AD, Byrne EM, Castelao E, Craddock N, Craig IW, Dannlowski U, Deary IJ, Degenhardt F, Forstner AJ, Gordon SD, Grabe HJ, Grove J, Hamilton SP, Hayward C, Heath AC, Hocking LJ, Homuth G, Hottenga JJ, Kloiber S, Krogh J, Landén M, Lang M, Levinson DF, Lichtenstein P, Lucae S, MacIntyre DJ, Madden P, Magnusson PKE, Martin NG, McIntosh AM, Middeldorp CM, Milaneschi Y, Montgomery GW, Mors O, Müller-Myhsok B, Nyholt DR, Oskarsson H, Owen MJ, Padmanabhan S, Penninx BWJH, Pergadia ML, Porteous DJ, Potash JB, Preisig M, Rivera M, Shi J, Shyn SI, Sigurdsson E, Smit JH, Smith BH, Stefansson H, Stefansson K, Strohmaier J, Sullivan PF, Thomson P, Thorgeirsson TE, Van der Auwera S, Weissman MM, CONVERGE Consortium, CARDIoGRAM Consortium, GERAD1 Consortium, Breen G, Lewis CM
- Issue date: 2017 Feb 15
- Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia.
- Authors: Ward J, Strawbridge RJ, Bailey MES, Graham N, Ferguson A, Lyall DM, Cullen B, Pidgeon LM, Cavanagh J, Mackay DF, Pell JP, O'Donovan M, Escott-Price V, Smith DJ
- Issue date: 2017 Nov 30
- Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
- Authors: Cross-Disorder Group of the Psychiatric Genomics Consortium
- Issue date: 2013 Apr 20
Related items
Showing items related by title, author, creator and subject.
-
Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorderDemontis, Ditte; Walters, Raymond K.; Rajagopal, Veera M.; Waldman, Irwin D.; Grove, Jakob; Als, Thomas D.; Dalsgaard, Søren; Ribasés, Marta; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Maria; et al. (Springer Science and Business Media LLC, 2021-01-25)Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10-10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.
-
Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorderDemontis, Ditte; Walters, Raymond K.; Rajagopal, Veera M.; Waldman, Irwin D.; Grove, Jakob; Als, Thomas D.; Dalsgaard, Søren; Ribasés, Marta; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Maria; et al. (Springer Science and Business Media LLC, 2021-01-25)Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR= 1.17). We find a higher SNP heritability for ADHD + DBDs (h2 SNP = 0.34) when compared to ADHD without DBDs (h2 SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.
-
An arts-informed study: a music therapists personal journey with attention-deficit hyperactivity disorder or ADHD and generalized anxiety disorderGerman, Brittany E. (2018-12)This arts-informed, first-person study examines how having a diagnosis of Attention- Deficit/Hyperactivity Disorder and Generalized Anxiety Disorder has affected a music therapists’ journey through her personal and professional life. The data used in this study includes: a) an analysis of referential musical improvisations based on my past experiences, my feelings in the present, and what I am hoping for in the future; (b) an analysis of paintings created in response to the musical improvisations; and (c) the personal experience of the researcher during the artistic creations. Through analysis of the data nine themes were found, three in each time period: past - chaos, hardship, and heartache; present - building self-confidence, emerging happiness, and hope; and future - acceptance, joy, and confidence. These themes provide insight into the changes in perception of the researcher’s disability.