Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD.
Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD.
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DOI：
10.1186/1471-2164-10-338
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发表时间：
2009-07-28
期刊：
影响因子：
4.4
通讯作者：
Bertranpetit J
中科院分区：
文献类型：
--
作者：
Bosch E;Laayouni H;Morcillo-Suarez C;Casals F;Moreno-Estrada A;Ferrer-Admetlla A;Gardner M;Rosa A;Navarro A;Comas D;Graffelman J;Calafell F;Bertranpetit J
众所周知，人类群体之间的连锁不平衡模式各不相同，具有显著的地理分层。间接关联研究经常利用基因周围的连锁不平衡，特别是在被认为更高的孤立群体中。在这里，我们探索了沿211个基因区域的连锁不平衡的数量和衰减随着物理距离的变化，其中大多数与复杂疾病有关，跨越39个HGDP-CEPH群体样本，特别关注被定义为分离物的群体。在每个基因区域和群体中，我们使用所有可能的单核苷酸多态(SNP)对之间的R2作为连锁不平衡的度量，并关注R2>0.8的SNP对的比例。虽然平均R2在大陆区域之间和大陆区域内都有显著差异，但更高比例的R2差异可以归因于大陆区域之间的差异(分别为2.8%和0.5%)。同样，尽管各大洲所有距离类别中R2>；0.8的SNP配对比例有很大差异，但除非洲和美洲外，各大洲内的SNP配对比例一般要同质得多。在所有距离类别中，相对于他们的大陆，唯一具有持续较高LD的孤立人口是卡拉什人(中亚)和苏瑞人(美洲)。此外，与同一块大陆上的非隔离人群相比，隔离人群中每个基因区域R2>；0.8的SNP配对比例仅略高。因此，隔离人群中需要进行基因分型的SNPs数量可能仅略少于非隔离人群。“隔离人群”的标签本身并不能保证在关联研究中有更高的基因分型效率，除了增加连锁不平衡以外的其他性质可能会使这些人群在遗传流行病学中变得有趣。
It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8. Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates. The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.
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影响因子：
56.9
作者：
Rosenberg, NA;Pritchard, JK;Feldman, MW
通讯作者：
Feldman, MW
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
5.4
作者：
HILL W G;ROBERTSON A
通讯作者：
ROBERTSON A
影响因子：
56.9
作者：
Hinds, DA;Stuve, LL;Cox, DR
通讯作者：
Cox, DR
影响因子：
56.9
作者：
McVean, GAT;Myers, SR;Donnelly, P
通讯作者：
Donnelly, P