The genetics of the mood disorder spectrum: genome-wide association analyses of over 185,000 cases and 439,000 controls
Abstract
Mood disorders affect 10-20% of the population, ranging from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of genetic risk factors between unipolar and bipolar mood disorders. We use data from the largest genome-wide association studies of major depression (MD) and bipolar disorder (BD) to investigate the molecular basis of the shared genetic liability to mood disorders. We meta-analysed the Psychiatric Genomics Consortium (PGC) MD and BD cohorts, and an additional MD cohort from UK Biobank (185,285 cases, 439,741 controls, non-overlapping N = 609,424). 73 loci reached genome-wide significance in the meta-analysis, with additional loci significant in subtype and depression-only analyses. More genome-wide significant loci from PGC MD (39/44, 89% of the PGC MD loci) than PGC BD (4/19, 21%) reached genome-wide significance in the meta-analysis. Genetic correlations calculated between MD and BD subtypes revealed that type II BD correlates strongly with MD. Integrating the results with systems biology information, we implicate pathways and neuronal subtypes which highlight similarities but also potential differences between MD and BD. Our results reflected MD more than BD, perhaps due to the larger sample size for MD, but also perhaps because depression is their predominant common feature. Overall, these results provide evidence for a genetic mood disorders spectrum.
Subject Area
- Biochemistry (11752)
- Bioengineering (8752)
- Bioinformatics (29200)
- Biophysics (14974)
- Cancer Biology (12096)
- Cell Biology (17411)
- Clinical Trials (138)
- Developmental Biology (9421)
- Ecology (14182)
- Epidemiology (2067)
- Evolutionary Biology (18308)
- Genetics (12245)
- Genomics (16803)
- Immunology (11869)
- Microbiology (28097)
- Molecular Biology (11594)
- Neuroscience (60969)
- Paleontology (451)
- Pathology (1871)
- Pharmacology and Toxicology (3238)
- Physiology (4959)
- Plant Biology (10427)
- Synthetic Biology (2886)
- Systems Biology (7340)
- Zoology (1651)