Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
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DOI：
10.1371/journal.pone.0028632
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Partners in Prevention HSV/HIV Transmission Study Team
中科院分区：
文献类型：
--
作者：
Lingappa JR;Petrovski S;Kahle E;Fellay J;Shianna K;McElrath MJ;Thomas KK;Baeten JM;Celum C;Wald A;de Bruyn G;Mullins JI;Nakku-Joloba E;Farquhar C;Essex M;Donnell D;Kiarie J;Haynes B;Goldstein D;Partners in Prevention HSV/HIV Transmission Study Team
宿主遗传因素可能是HIV-1性获得的重要决定因素。我们进行了一项全基因组关联研究（GWAS），在非洲HIV-1血清不一致的异性恋夫妇队列的背景下，修改HIV-1获得和病毒控制的宿主遗传变异。为了尽量减少对HIV-1风险的错误分类，我们使用包括血浆HIV-1浓度、性别和避孕套使用在内的数据对HIV-1暴露进行了量化。我们通过量化的HIV-1暴露风险将没有HIV-1血清转换的夫妇与血清转换的夫妇配对。对来自496名HIV-1感染者和302名HIV-1暴露未感染者的798份样本进行单核苷酸多态性（SNPs）的Logistic回归，以确定与HIV-1获得相关的因素。此外，使用来自HIV-1感染个体的子集（n=403）的SNP数据进行线性回归分析，以鉴定预测血浆HIV-1浓度的因素。 校正多重比较后，没有SNPs与HIV-1感染状态或血浆HIV-1浓度显著相关。控制HIV-1暴露的GWAS没有识别出影响HIV-1获得的常见宿主基因型。替代策略，如大规模测序，以确定低频率的变化，应考虑确定新的宿主遗传预测HIV-1的收购。
Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use. We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations. After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations. This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition.
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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：
56.3
作者：
Boily, Marie-Claude;Baggaley, Rebecca F.;Wang, Lei;Masse, Benoit;White, Richard G.;Hayes, Richard J.;Alary, Michel
通讯作者：
Alary, Michel
影响因子：
30.8
作者：
Bhangale, Tushar R.;Rieder, Mark J.;Nickerson, Deborah A.
通讯作者：
Nickerson, Deborah A.
影响因子：
3.2
作者：
Malik, S;Arias, M;Schurr, E
通讯作者：
Schurr, E
影响因子：
3.7
作者：
Lingappa JR;Hughes JP;Wang RS;Baeten JM;Celum C;Gray GE;Stevens WS;Donnell D;Campbell MS;Farquhar C;Essex M;Mullins JI;Coombs RW;Rees H;Corey L;Wald A;Partners in Prevention HSV/HIV Transmission Study Team
通讯作者：
Partners in Prevention HSV/HIV Transmission Study Team