Y A Kim1, H J Choi, J Y Lee, B G Han, C S Shin, N H Cho. 1. Department of Internal Medicine, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul, 110-744, Korea.
Abstract
SUMMARY: Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs. INTRODUCTION: Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples. METHODS: A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis. RESULTS: Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta). CONCLUSION: Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.
SUMMARY: Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs. INTRODUCTION: Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples. METHODS: A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis. RESULTS: Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta). CONCLUSION: Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.
Authors: Annie W C Kung; Su-Mei Xiao; Stacey Cherny; Gloria H Y Li; Yi Gao; Gloria Tso; Kam S Lau; Keith D K Luk; Jian-min Liu; Bin Cui; Min-Jia Zhang; Zhen-lin Zhang; Jin-wei He; Hua Yue; Wia-bo Xia; Lian-mei Luo; Shu-li He; Douglas P Kiel; David Karasik; Yi-Hsiang Hsu; L Adrienne Cupples; Serkalem Demissie; Unnur Styrkarsdottir; Bjarni V Halldorsson; Gunnar Sigurdsson; Unnur Thorsteinsdottir; Kari Stefansson; J Brent Richards; Guangju Zhai; Nicole Soranzo; Ana Valdes; Tim D Spector; Pak C Sham Journal: Am J Hum Genet Date: 2010-01-21 Impact factor: 11.025
Authors: Kelly A Frazer; Dennis G Ballinger; David R Cox; David A Hinds; Laura L Stuve; Richard A Gibbs; John W Belmont; Andrew Boudreau; Paul Hardenbol; Suzanne M Leal; Shiran Pasternak; David A Wheeler; Thomas D Willis; Fuli Yu; Huanming Yang; Changqing Zeng; Yang Gao; Haoran Hu; Weitao Hu; Chaohua Li; Wei Lin; Siqi Liu; Hao Pan; Xiaoli Tang; Jian Wang; Wei Wang; Jun Yu; Bo Zhang; Qingrun Zhang; Hongbin Zhao; Hui Zhao; Jun Zhou; Stacey B Gabriel; Rachel Barry; Brendan Blumenstiel; Amy Camargo; Matthew Defelice; Maura Faggart; Mary Goyette; Supriya Gupta; Jamie Moore; Huy Nguyen; Robert C Onofrio; Melissa Parkin; Jessica Roy; Erich Stahl; Ellen Winchester; Liuda Ziaugra; David Altshuler; Yan Shen; Zhijian Yao; Wei Huang; Xun Chu; Yungang He; Li Jin; Yangfan Liu; Yayun Shen; Weiwei Sun; Haifeng Wang; Yi Wang; Ying Wang; Xiaoyan Xiong; Liang Xu; Mary M Y Waye; Stephen K W Tsui; Hong Xue; J Tze-Fei Wong; Luana M Galver; Jian-Bing Fan; Kevin Gunderson; Sarah S Murray; Arnold R Oliphant; Mark S Chee; Alexandre Montpetit; Fanny Chagnon; Vincent Ferretti; Martin Leboeuf; Jean-François Olivier; Michael S Phillips; Stéphanie Roumy; Clémentine Sallée; Andrei Verner; Thomas J Hudson; Pui-Yan Kwok; Dongmei Cai; Daniel C Koboldt; Raymond D Miller; Ludmila Pawlikowska; Patricia Taillon-Miller; Ming Xiao; Lap-Chee Tsui; William Mak; You Qiang Song; Paul K H Tam; Yusuke Nakamura; Takahisa Kawaguchi; Takuya Kitamoto; Takashi Morizono; Atsushi Nagashima; Yozo Ohnishi; Akihiro Sekine; Toshihiro Tanaka; Tatsuhiko Tsunoda; Panos Deloukas; Christine P Bird; Marcos Delgado; Emmanouil T Dermitzakis; Rhian Gwilliam; Sarah Hunt; Jonathan Morrison; Don Powell; Barbara E Stranger; Pamela Whittaker; David R Bentley; Mark J Daly; Paul I W de Bakker; Jeff Barrett; Yves R Chretien; Julian Maller; Steve McCarroll; Nick Patterson; Itsik Pe'er; Alkes Price; Shaun Purcell; Daniel J Richter; Pardis Sabeti; Richa Saxena; Stephen F Schaffner; Pak C Sham; Patrick Varilly; David Altshuler; Lincoln D Stein; Lalitha Krishnan; Albert Vernon Smith; Marcela K Tello-Ruiz; Gudmundur A Thorisson; Aravinda Chakravarti; Peter E Chen; David J Cutler; Carl S Kashuk; Shin Lin; Gonçalo R Abecasis; Weihua Guan; Yun Li; Heather M Munro; Zhaohui Steve Qin; Daryl J Thomas; Gilean McVean; Adam Auton; Leonardo Bottolo; Niall Cardin; Susana Eyheramendy; Colin Freeman; Jonathan Marchini; Simon Myers; Chris Spencer; Matthew Stephens; Peter Donnelly; Lon R Cardon; Geraldine Clarke; David M Evans; Andrew P Morris; Bruce S Weir; Tatsuhiko Tsunoda; James C Mullikin; Stephen T Sherry; Michael Feolo; Andrew Skol; Houcan Zhang; Changqing Zeng; Hui Zhao; Ichiro Matsuda; Yoshimitsu Fukushima; Darryl R Macer; Eiko Suda; Charles N Rotimi; Clement A Adebamowo; Ike Ajayi; Toyin Aniagwu; Patricia A Marshall; Chibuzor Nkwodimmah; Charmaine D M Royal; Mark F Leppert; Missy Dixon; Andy Peiffer; Renzong Qiu; Alastair Kent; Kazuto Kato; Norio Niikawa; Isaac F Adewole; Bartha M Knoppers; Morris W Foster; Ellen Wright Clayton; Jessica Watkin; Richard A Gibbs; John W Belmont; Donna Muzny; Lynne Nazareth; Erica Sodergren; George M Weinstock; David A Wheeler; Imtaz Yakub; Stacey B Gabriel; Robert C Onofrio; Daniel J Richter; Liuda Ziaugra; Bruce W Birren; Mark J Daly; David Altshuler; Richard K Wilson; Lucinda L Fulton; Jane Rogers; John Burton; Nigel P Carter; Christopher M Clee; Mark Griffiths; Matthew C Jones; Kirsten McLay; Robert W Plumb; Mark T Ross; Sarah K Sims; David L Willey; Zhu Chen; Hua Han; Le Kang; Martin Godbout; John C Wallenburg; Paul L'Archevêque; Guy Bellemare; Koji Saeki; Hongguang Wang; Daochang An; Hongbo Fu; Qing Li; Zhen Wang; Renwu Wang; Arthur L Holden; Lisa D Brooks; Jean E McEwen; Mark S Guyer; Vivian Ota Wang; Jane L Peterson; Michael Shi; Jack Spiegel; Lawrence M Sung; Lynn F Zacharia; Francis S Collins; Karen Kennedy; Ruth Jamieson; John Stewart Journal: Nature Date: 2007-10-18 Impact factor: 49.962
Authors: Ye Seul Bae; Sun-Wha Im; Mi So Kang; Jin Hee Kim; Soon Hang Lee; Be Long Cho; Jin Ho Park; You-Seon Nam; Ho-Young Son; San Deok Yang; Joohon Sung; Kwang Ho Oh; Jae Moon Yun; Jong Il Kim Journal: Genomics Inform Date: 2016-06-30