Study Finds 15 Genes, 64 Loci Associated With Bipolar Disorder

A recent association study found that 15 genes and at least 4 targets potentially responsive to pharmacologic treatment are tied to bipolar disorder. The authors published their findings in Nature Genetics.

The researchers conducted a genome-wide association study (GWAS) meta-analysis of 57 bipolar disorder cohorts in Europe, North America, and Australia. The study included 41,917 individuals with bipolar disorder and 371,549 control group participants of European descent. The study looked at genotype and phenotype data.

The researchers found 64 independent loci associated with bipolar disorder. Of those, 33 are novel discoveries. A genome-wide analysis using MAGMA [Multi-marker Analysis of GenoMic Annotation], a tool that allows for gene and gene-set analysis of GWAS data, found “significant enrichment” of bipolar disorder associations in 161 genes. Traits such as sleep disturbances, alcohol use, smoking, and mood instability were found to have “modest but significant” genetic correlations to bipolar disorder.

“Our analyses confirmed that [bipolar disorder] is a highly polygenic disorder, with an estimated 8,600 variants explaining 90% of its h²_SNP,” the researchers stated. “These new data advance our understanding of the biological etiology of BD and prioritize a set of candidate genes for functional follow-up experiments. Several lines of evidence converge on the involvement of calcium channel signaling, providing a promising avenue for future therapeutic development.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Mullins N, Forstner AJ, O’Connell KS, et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet. 2021;53(6):817-829. doi:10.1038/s41588-021-00857-4