Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
paper
Cited
Public
Unavailable
- Authors
- Psychiatric GWAS Consortium Bipolar Disorder Working Group
- Year
- 2011
- Journal
- Nature genetics
- PMID
- 21926972
- DOI
- 10.1038/ng.943
- PMCID
- PMC3637176
We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 Γ 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
Results are shown as βlog10(P value) for genotyped and imputed SNPs. The most associated SNP in the primary analysis is shown as the small purple triangle. The most associated SNP in the combined analysis is shown as the large purple triangle. The color of the remaining markers reflects r2 with the most associated SNP. The recombination rate from CEU HapMap (second y axis) is plotted in light blue.
LLM interpretation
These are two LocusZoom plots showing genetic association results for SNPs on chromosomes 12 and 11. The x-axes represent genomic positions (Mb), while the primary y-axis shows association strength as $-\log_{10}(P\text{ value})$ and the secondary y-axis shows the recombination rate in light blue. Markers are color-coded by linkage disequilibrium ($r^2$) relative to the lead SNPs (rs4765913 and rs12576775), which are highlighted as purple triangles.
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