Identification of evidence suggestive of an association with peripheral arterial disease at the OSBPL10 locus by genome-wide investigation in the Japanese population

Aim: peripheral arterial disease (pad) is a common cause of cardiovascular morbidity and an independent predictor of cardiovascular mortality. however,little is known about the genetic basis of pad. to elucidate this,we performed a two-staged genome-wide association study in japanese individuals. methods: we initially tested 222,285 single-nucleotide polymorphisms (snps). after the first screening in a panel of 195 pad cases and 1,358 controls,2,696 snps (1.2%) were further genotyped in the second screening using another panel of 699 pad cases and 1540 controls. in both screenings,controls were subjects affected with some diseases other than pad. results: when analyzed in the combined panel,the strongest signal of pad association was observed at rs1902341 in the intron of osbpl10 (p = 4.7e-7 for trend test; or = 1.31,95% ci 1.18-1.46). also,pad was modestly associated at several other loci such as rs2554503 in csmd1 (p = 5.7e-5; or = 1.32,95% ci 1.15-1.51) or rs235243 in vsp13d (p = 0.04; or = 1.18,95% ci 1.01-1.37). conclusion: our genome-wide exploration identified suggestive evidence of pad association at the osbpl10 locus. because the association has not reached a genome-wide significant level,further replication study is warranted for verification in the japanese population.