Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder
ABSTRACT
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10−9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10−9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
ABBREVIATIONS
- BD
- Bipolar Disorder
- SCZ
- Schizophrenia
- GWAS
- Genome-wide Association Study
- SNP
- Single Nucleotide Polymorphism
- MAF
- Minor Allele Frequency
- OR
- Odds Ratio
- SD
- Standard Deviation
- CI
- Confidence Interval
- eQTL
- expression Quantitative Trait Locus
- GAIN-NIMH
- Genetic Association Information Network - National institute of Mental Health
- WTCCC
- Wellcome Trust Case Control Consortium
- STEP-BD
- Systematic Treatment Enhancement Program for Bipolar Disorder
- TGEN
- Translational Genomics Research Institute
- ConLiGen
- The International Consortium on Lithium Genetics
- BoMA
- Bonn-Mannheim
- dbGaP
- Database of Genotypes and Phenotypes
- NCP
- Non-Centrality Parameter
- GRR
- Genotype-Relative Risk
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