scholarly journals Genetic predictors of risk and resilience in psychiatric disorders: A cross-disorder genome-wide association study of functional impairment in major depressive disorder, bipolar disorder, and schizophrenia

2013 ◽  
Vol 162 (8) ◽  
pp. 779-788 ◽  
Author(s):  
Lauren M. McGrath ◽  
Marilyn C. Cornelis ◽  
Phil H. Lee ◽  
Elise B. Robinson ◽  
Laramie E. Duncan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Functional Impairment ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Risk And Resilience ◽  
Major Depressive ◽  
Genetic Predictors ◽  
Genome Wide

scholarly journals The genetics of the mood disorder spectrum: genome-wide association analyses of over 185,000 cases and 439,000 controls

2018 ◽  
Author(s):  
Jonathan R. I. Coleman ◽  
Héléna A. Gaspar ◽  
Julien Bryois ◽  
Gerome Breen ◽  
◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Major Depression ◽  
Depressive Disorder ◽  
Mood Disorders ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Major Depressive ◽  
Genome Wide ◽  
Genome Wide Significance

AbstractBackgroundMood 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.

scholarly journals Genome-wide association study of recurrent early-onset major depressive disorder

2010 ◽  
Vol 16 (2) ◽  
pp. 193-201 ◽  
Author(s):  
J Shi ◽  
J B Potash ◽  
J A Knowles ◽  
M M Weissman ◽  
W Coryell ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Association Study ◽  
Early Onset ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Major Depressive ◽  
Genome Wide

scholarly journals Genome-wide association study of circadian rhythmicity in 71 500 UK Biobank participants and polygenic association with mood instability

2018 ◽  
Author(s):  
Amy Ferguson ◽  
Laura M. Lyall ◽  
Joey Ward ◽  
Rona J. Strawbridge ◽  
Breda Cullen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Circadian Rhythmicity ◽  
Genome Wide Association ◽  
Uk Biobank ◽  
Major Depressive ◽  
Mood Instability ◽  
Genome Wide

AbstractBackgroundCircadian rhythms are fundamental to health and are particularly important for mental wellbeing. Disrupted rhythms of rest and activity are recognised as risk factors for major depressive disorder and bipolar disorder.MethodsWe conducted a genome-wide association study (GWAS) of low relative amplitude (RA), an objective measure of circadian rhythmicity derived from the accelerometer data of 71 500 UK Biobank participants. Polygenic risk scores (PRS) for low RA were used to investigate potential associations with psychiatric phenotypes.OutcomesTwo independent genetic loci were associated with low RA, within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25 Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a locus within Meis Homeobox 1 (MEIS1). There were no significant genetic correlations between low RA and any of the psychiatric phenotypes assessed. However, PRS for low RA was significantly associated with mood instability across multiple PRS thresholds (at PRS threshold 0·05: OR=1·02, 95% CI=1·01-1·02, p=9·6×10−5), and with major depressive disorder (at PRS threshold 0·1: OR=1·03, 95% CI=1·01-1·05, p=0·025) and neuroticism (at PRS threshold 0·5: Beta=0·02, 95% CI=0·007-0·04, p=0·021).InterpretationOverall, our findings contribute new knowledge on the complex genetic architecture of circadian rhythmicity and suggest a putative biological link between disrupted circadian function and mood disorder phenotypes, particularly mood instability, but also major depressive disorder and neuroticism.

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