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New preprint from @PGCgenetics - PGC3 bipolar disorder (BD) GWAS identifies 64 GW sig loci 2020.09.17.20187054v1
Highlights: 1) >40k cases from European ancestries, 33 novel loci, inflection point (where increase in sample size results in a ~linear increase in novel loci) now reached!
2) Strong role for calcium signaling in BD - enrichment in gene targets of calcium channel blockers and antiepileptics. Opportunities for validation and future drug repurposing?
3) 15 genes linked to BD via predicted brain/blood expression, including druggable genes eg. HTR6, MCHR1, DCLK3, FURIN - promising candidates for functional experiments!
4) PRS explain up to 6.6% phenotypic variance in European ancestry cohorts, improved performance in East Asian and African cohorts compared to previous PGC GWAS, but no clinical utility at present
5) Many variants affect BD and related traits eg sleep, substance use.
As always, GWAS summary statistics will be on PGC website upon publication. Huge thanks to >300 co-authors for contributing to this effort, and to co-first authors @NiamhAMullins and Andreas Forstner! To join us for the next wave of BD GWAS (with a focus on diverse ancestries)
