Genome-wide and fine-resolution association analysis of malaria in West Africa.
Genome-wide and fine-resolution association analysis of malaria in West Africa.
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DOI：
10.1038/ng.388
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发表时间：
2009-06
期刊：
影响因子：
30.8
通讯作者：
Kwiatkowski, Dominic P.
中科院分区：
文献类型：
--
作者：
Jallow, Muminatou;Teo, Yik Ying;Small, Kerrin S.;Rockett, Kirk A.;Deloukas, Panos;Clark, Taane G.;Kivinen, Katja;Bojang, Kalifa A.;Conway, David J.;Pinder, Margaret;Sirugo, Giorgio;Sisay-Joof, Fatou;Usen, Stanley;Auburn, Sarah;Bumpstead, Suzannah J.;Campino, Susana;Coffey, Alison;Dunham, Andrew;Fry, Andrew E.;Green, Angela;Gwilliam, Rhian;Hunt, Sarah E.;Inouye, Michael;Jeffreys, Anna E.;Mendy, Alieu;Palotie, Aarno;Potter, Simon;Ragoussis, Jiannis;Rogers, Jane;Rowlands, Kate;Somaskantharajah, Elilan;Whittaker, Pamela;Widden, Claire;Donnelly, Peter;Howie, Bryan;Marchini, Jonathan;Morris, Andrew;SanJoaquin, Miguel;Achidi, Eric Akum;Agbenyega, Tsiri;Allen, Angela;Amodu, Olukemi;Corran, Patrick;Djimde, Abdoulaye;Dolo, Amagana;Doumbo, Ogobara K.;Drakeley, Chris;Dunstan, Sarah;Evans, Jennifer;Farrar, Jeremy;Fernando, Deepika;Hien, Tran Tinh;Horstmann, Rolf D.;Ibrahim, Muntaser;Karunaweera, Nadira;Kokwaro, Gilbert;Koram, Kwadwo A.;Lemnge, Martha;Makani, Julie;Marsh, Kevin;Michon, Pascal;Modiano, David;Molyneux, Malcolm E.;Mueller, Ivo;Parker, Michael;Peshu, Norbert;Plowe, Christopher V.;Puijalon, Odile;Reeder, John;Reyburn, Hugh;Riley, Eleanor M.;Sakuntabhai, Anavaj;Singhasivanon, Pratap;Sirima, Sodiomon;Tall, Adama;Taylor, Terrie E.;Thera, Mahamadou;Troye-Blomberg, Marita;Williams, Thomas N.;Wilson, Michael;Kwiatkowski, Dominic P.
我们报告了一项关于冈比亚严重疟疾的全基因组关联(GWA)研究。最初的GWA扫描包括2,500名儿童在Affymetrix 500K基因芯片上的基因分型，复制研究包括3,400名儿童。我们利用这一点来检查GWA方法在非洲的表现。我们发现了相当大的群体分层，而且由于弱连锁不平衡(LD)，已知的疟疾耐药基因座的关联信号也大大减弱。为了探索低LD问题的可能解决方案，我们将重点放在HBS基因座上，对62名冈比亚人的基因组这一区域进行测序，然后使用这些数据在GWA样本中进行多点推测。这增加了关联信号，从P=4×10−7增加到P=4×10−14，信号的峰恰好位于HbS因果变量。我们的发现提供了原则证据，即基于特定于人群的测序数据的精细分辨率多点归因法可以显著增强真实的GWA信号，并能够对非洲人群中的因果变异进行精细定位。
We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10−7 to P = 4 × 10−14, with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
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影响因子：
3.5
作者：
Fry AE;Griffiths MJ;Auburn S;Diakite M;Forton JT;Green A;Richardson A;Wilson J;Jallow M;Sisay-Joof F;Pinder M;Peshu N;Williams TN;Marsh K;Molyneux ME;Taylor TE;Rockett KA;Kwiatkowski DP
通讯作者：
Kwiatkowski DP
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
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：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
30.8
作者：
Bhangale, Tushar R.;Rieder, Mark J.;Nickerson, Deborah A.
通讯作者：
Nickerson, Deborah A.