Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder
ABSTRACT
Bipolar disorder is a highly heritable psychiatric disorder that features episodes of mania and depression. We performed the largest genome-wide association study to date, including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 881 sentinel variants at loci with P<1×10−4 in an independent sample of 9,412 cases and 137,760 controls. In the combined analysis, 30 loci achieved genome-wide significance including 20 novel loci. These significant loci contain genes encoding ion channels and neurotransmitter transporters (CACNA1C, GRIN2A, SCN2A, SLC4A1), synaptic components (RIMS1, ANK3), immune and energy metabolism components, and multiple potential therapeutic targets for mood stabilizer drugs. Bipolar disorder type I (depressive and manic episodes; ~73% of our cases) is strongly genetically correlated with schizophrenia whereas type II (depressive and hypomanic episodes; ~17% of our cases) correlated more with major depression. Furthermore, bipolar disorder has a positive genetic correlation with educational attainment yet has no significant genetic correlation with intelligence. These findings address key clinical questions and provide potential new biological mechanisms for bipolar disorder.
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