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

Hiroshi Koriyama, Hironori Nakagami, Tomohiro Katsuya, Ken Sugimoto, Hidetoshi Yamashita, Yoichi Takami, Shiro Maeda, Michiaki Kubo, Atsushi Takahashi, Yusuke Nakamura, Toshio Ogihara, Hiromi Rakugi, Yasufumi Kaneda, Ryuichi Morishita

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1054-1062
Number of pages9
JournalJournal of atherosclerosis and thrombosis
Volume17
Issue number10
DOIs
Publication statusPublished - 2010

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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