Non-synonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association.
Non-synonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association.
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DOI：
10.1371/journal.pone.0013574
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发表时间：
2010-10-22
期刊：
影响因子：
3.7
通讯作者：
Butte AJ
中科院分区：
文献类型：
--
作者：
Chen R;Davydov EV;Sirota M;Butte AJ
通过全基因组关联研究 (GWAS)，已在 300 多种疾病和性状中鉴定出许多 DNA 变异。有些已经使用深度测序进行了验证，但很少有经过功能验证，主要集中在非同义编码 SNP (nsSNP)。同义编码 SNP (sSNP) 和其他非编码 SNP 是否会导致与 nsSNP 一样高的比值比，这是一个悬而未决的问题。我们对从 2,113 份研究人类遗传关联的出版物中筛选出的 21,429 个疾病-SNP 关联进行了广泛的调查，发现 nsSNP 和 sSNP 与疾病关联的可能性和效应大小相似。第一个内含子中第 80 个碱基周围与疾病相关的 SNP 的富集可能为功能研究中优先考虑内含子 SNP 提供了一种有效的方法。我们进一步发现，疾病关联的可能性与不同类型的 SNP 的效应大小呈正相关，并且 3'非翻译区域（例如 microRNA 结合位点）的 SNP 可能尚未得到充分研究。我们的结果表明，sSNP 同样可能参与疾病机制，因此我们建议还应通过功能研究来检查从 GWAS 中发现的 sSNP。
Many DNA variants have been identified on more than 300 diseases and traits using Genome-Wide Association Studies (GWASs). Some have been validated using deep sequencing, but many fewer have been validated functionally, primarily focused on non-synonymous coding SNPs (nsSNPs). It is an open question whether synonymous coding SNPs (sSNPs) and other non-coding SNPs can lead to as high odds ratios as nsSNPs. We conducted a broad survey across 21,429 disease-SNP associations curated from 2,113 publications studying human genetic association, and found that nsSNPs and sSNPs shared similar likelihood and effect size for disease association. The enrichment of disease-associated SNPs around the 80th base in the first introns might provide an effective way to prioritize intronic SNPs for functional studies. We further found that the likelihood of disease association was positively associated with the effect size across different types of SNPs, and SNPs in the 3′untranslated regions, such as the microRNA binding sites, might be under-investigated. Our results suggest that sSNPs are just as likely to be involved in disease mechanisms, so we recommend that sSNPs discovered from GWAS should also be examined with functional studies.
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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：
168.9
作者：
Ashley, Euan A.;Butte, Atul J.;Wheeler, Matthew T.;Chen, Rong;Klein, Teri E.;Dewey, Frederick E.;Dudley, Joel T.;Ormond, Kelly E.;Pavlovic, Aleksandra;Morgan, Alexander A.;Pushkarev, Dmitry;Neff, Norma F.;Hudgins, Louanne;Gong, Li;Hodges, Laura M.;Berlin, Dorit S.;Thorn, Caroline F.;Sangkuhl, Katrin;Hebert, Joan M.;Woon, Mark;Sagreiya, Hersh;Whaley, Ryan;Knowles, Joshua W.;Chou, Michael F.;Thakuria, Joseph V.;Rosenbaum, Abraham M.;Zaranek, Alexander Wait;Church, George M.;Greely, Henry T.;Quake, Stephen R.;Altman, Russ B.
通讯作者：
Altman, Russ B.
稀有变体会产生整个基因组的关联。
影响因子：
9.8
作者：
Dickson SP;Wang K;Krantz I;Hakonarson H;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
3.5
作者：
Capon, F;Allen, MH;Trembath, RC
通讯作者：
Trembath, RC
DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.