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

doi:10.5551/jat.4291

Original Article

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

Author information

Hiroshi Koriyama
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
Hironori Nakagami
Division of Gene Therapy Science, Osaka University Graduate School of Medicine.
Tomohiro Katsuya
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine.
Ken Sugimoto
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
Hidetoshi Yamashita
Division of Gene Therapy Science, Osaka University Graduate School of Medicine.
Yoichi Takami
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
Shiro Maeda
Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN.
Michiaki Kubo
Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN.
Atsushi Takahashi
Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN.
Yusuke Nakamura
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo.
Toshio Ogihara
Osaka General Medical Center, Osaka Prefectural Hospital Organization.
Hiromi Rakugi
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine.
Yasufumi Kaneda
Division of Gene Therapy Science, Osaka University Graduate School of Medicine.
Ryuichi Morishita
Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine.

Keywords: Peripheral arterial disease, Genome-wide association study, OSBPL10

JOURNAL OPEN ACCESS

2010 Volume 17 Issue 10 Pages 1054-1062

DOI https://doi.org/10.5551/jat.4291

View "Advance Publication" version (July 2, 2010).

Details

Abstract

Aim: Peripheral arterial disease (PAD) is a common cause of cardiovascular morbidity and an inde-pendent 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 indi-viduals.
Methods: We initially tested 222,285 single-nucleotide polymorphisms (SNPs). After the first screen-ing 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.

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