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.
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.
Authors: Yun Ju Sung; Lisa de Las Fuentes; Thomas W Winkler; Daniel I Chasman; Amy R Bentley; Aldi T Kraja; Ioanna Ntalla; Helen R Warren; Xiuqing Guo; Karen Schwander; Alisa K Manning; Michael R Brown; Hugues Aschard; Mary F Feitosa; Nora Franceschini; Yingchang Lu; Ching-Yu Cheng; Xueling Sim; Dina Vojinovic; Jonathan Marten; Solomon K Musani; Tuomas O Kilpeläinen; Melissa A Richard; Stella Aslibekyan; Traci M Bartz; Rajkumar Dorajoo; Changwei Li; Yongmei Liu; Tuomo Rankinen; Albert Vernon Smith; Salman M Tajuddin; Bamidele O Tayo; Wei Zhao; Yanhua Zhou; Nana Matoba; Tamar Sofer; Maris Alver; Marzyeh Amini; Mathilde Boissel; Jin Fang Chai; Xu Chen; Jasmin Divers; Ilaria Gandin; Chuan Gao; Franco Giulianini; Anuj Goel; Sarah E Harris; Fernando P Hartwig; Meian He; Andrea R V R Horimoto; Fang-Chi Hsu; Anne U Jackson; Candace M Kammerer; Anuradhani Kasturiratne; Pirjo Komulainen; Brigitte Kühnel; Karin Leander; Wen-Jane Lee; Keng-Hung Lin; Jian'an Luan; Leo-Pekka Lyytikäinen; Colin A McKenzie; Christopher P Nelson; Raymond Noordam; Robert A Scott; Wayne H H Sheu; Alena Stančáková; Fumihiko Takeuchi; Peter J van der Most; Tibor V Varga; Robert J Waken; Heming Wang; Yajuan Wang; Erin B Ware; Stefan Weiss; Wanqing Wen; Lisa R Yanek; Weihua Zhang; Jing Hua Zhao; Saima Afaq; Tamuno Alfred; Najaf Amin; Dan E Arking; Tin Aung; R Graham Barr; Lawrence F Bielak; Eric Boerwinkle; Erwin P Bottinger; Peter S Braund; Jennifer A Brody; Ulrich Broeckel; Brian Cade; Archie Campbell; Mickaël Canouil; Aravinda Chakravarti; Massimiliano Cocca; Francis S Collins; John M Connell; Renée de Mutsert; H Janaka de Silva; Marcus Dörr; Qing Duan; Charles B Eaton; Georg Ehret; Evangelos Evangelou; Jessica D Faul; Nita G Forouhi; Oscar H Franco; Yechiel Friedlander; He Gao; Bruna Gigante; C Charles Gu; Preeti Gupta; Saskia P Hagenaars; Tamara B Harris; Jiang He; Sami Heikkinen; Chew-Kiat Heng; Albert Hofman; Barbara V Howard; Steven C Hunt; Marguerite R Irvin; Yucheng Jia; Tomohiro Katsuya; Joel Kaufman; Nicola D Kerrison; Chiea Chuen Khor; Woon-Puay Koh; Heikki A Koistinen; Charles B Kooperberg; Jose E Krieger; Michiaki Kubo; Zoltan Kutalik; Johanna Kuusisto; Timo A Lakka; Carl D Langefeld; Claudia Langenberg; Lenore J Launer; Joseph H Lee; Benjamin Lehne; Daniel Levy; Cora E Lewis; Yize Li; Sing Hui Lim; Ching-Ti Liu; Jianjun Liu; Jingmin Liu; Yeheng Liu; Marie Loh; Kurt K Lohman; Tin Louie; Reedik Mägi; Koichi Matsuda; Thomas Meitinger; Andres Metspalu; Lili Milani; Yukihide Momozawa; Thomas H Mosley; Mike A Nalls; Ubaydah Nasri; Jeff R O'Connell; Adesola Ogunniyi; Walter R Palmas; Nicholette D Palmer; James S Pankow; Nancy L Pedersen; Annette Peters; Patricia A Peyser; Ozren Polasek; David Porteous; Olli T Raitakari; Frida Renström; Treva K Rice; Paul M Ridker; Antonietta Robino; Jennifer G Robinson; Lynda M Rose; Igor Rudan; Charumathi Sabanayagam; Babatunde L Salako; Kevin Sandow; Carsten O Schmidt; Pamela J Schreiner; William R Scott; Peter Sever; Mario Sims; Colleen M Sitlani; Blair H Smith; Jennifer A Smith; Harold Snieder; John M Starr; Konstantin Strauch; Hua Tang; Kent D Taylor; Yik Ying Teo; Yih Chung Tham; André G Uitterlinden; Melanie Waldenberger; Lihua Wang; Ya Xing Wang; Wen Bin Wei; Gregory Wilson; Mary K Wojczynski; Yong-Bing Xiang; Jie Yao; Jian-Min Yuan; Alan B Zonderman; Diane M Becker; Michael Boehnke; Donald W Bowden; John C Chambers; Yii-Der Ida Chen; David R Weir; Ulf de Faire; Ian J Deary; Tõnu Esko; Martin Farrall; Terrence Forrester; Barry I Freedman; Philippe Froguel; Paolo Gasparini; Christian Gieger; Bernardo Lessa Horta; Yi-Jen Hung; Jost Bruno Jonas; Norihiro Kato; Jaspal S Kooner; Markku Laakso; Terho Lehtimäki; Kae-Woei Liang; Patrik K E Magnusson; Albertine J Oldehinkel; Alexandre C Pereira; Thomas Perls; Rainer Rauramaa; Susan Redline; Rainer Rettig; Nilesh J Samani; James Scott; Xiao-Ou Shu; Pim van der Harst; Lynne E Wagenknecht; Nicholas J Wareham; Hugh Watkins; Ananda R Wickremasinghe; Tangchun Wu; Yoichiro Kamatani; Cathy C Laurie; Claude Bouchard; Richard S Cooper; Michele K Evans; Vilmundur Gudnason; James Hixson; Sharon L R Kardia; Stephen B Kritchevsky; Bruce M Psaty; Rob M van Dam; Donna K Arnett; Dennis O Mook-Kanamori; Myriam Fornage; Ervin R Fox; Caroline Hayward; Cornelia M van Duijn; E Shyong Tai; Tien Yin Wong; Ruth J F Loos; Alex P Reiner; Charles N Rotimi; Laura J Bierut; Xiaofeng Zhu; L Adrienne Cupples; Michael A Province; Jerome I Rotter; Paul W Franks; Kenneth Rice; Paul Elliott; Mark J Caulfield; W James Gauderman; Patricia B Munroe; Dabeeru C Rao; Alanna C Morrison Journal: Hum Mol Genet Date: 2019-08-01 Impact factor: 6.150
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