PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry
Platelets are mediators of cardiovascular disease and are regulated by complex sets of interacting genes. To reveal new regulatory loci for platelet count (PLT), we performed genome-wide association studies (GWAS) in 20,218 Bangladeshi (BAN) and 9,198 Pakistani (PAK) individuals from the Genes and Health study. Most significantly associated loci (p <5 x10-8) replicated findings in prior transethnic GWAS. However, the BAN locus defined by rs946528 (chr1:46019890) did not associate with PLT in the PAK analysis but was in the same linkage disequilibrium block as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning eight coding genes. Functional annotation, mapping to megakaryocyte regulatory regions and colocalization with whole blood eQTLs identified the most likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase, widely linked elsewhere to adverse cardiovascular phenotypes.