Proper analysis of secondary phenotype data in case-control association studies.
Proper analysis of secondary phenotype data in case-control association studies.
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DOI：
10.1002/gepi.20377
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发表时间：
2009-04
影响因子：
2.1
通讯作者：
Zeng, D.
中科院分区：
文献类型：
--
作者：
Lin, D. Y.;Zeng, D.
关键词：
病例对照关联研究经常收集大量关于次要表型的信息，次要表型是病例对照状态以外的数量或质量性状。探索次级表型可以对生物学途径产生有价值的见解，并识别影响直接感兴趣的表型的遗传变异。所有关于次要表型的出版物都使用了标准的统计方法，如数量性状的最小二乘回归。由于病例和对照之间的选择概率不相等，病例对照样本不是来自一般人群的随机样本。因此，对次级表型数据的标准统计分析可能会产生极大的误导。虽然可以通过单独分析病例和对照组或将病例-对照状态作为协变量纳入模型来避免抽样偏倚，但病例组和对照组中次要表型与遗传变异之间的关联可能与一般人群中的关联完全不同。在这篇文章中，我们提出了新的统计方法，适当地反映了病例对照抽样分析的次要表型数据。新方法提供了遗传效应的无偏估计和假阳性率的准确控制，同时最大限度地提高统计功效。我们证明了标准方法的缺陷和新方法的优点，分析和数值。相关软件可在我们的网站上找到。
Case-control association studies often collect extensive information on secondary phenotypes, which are quantitative or qualitative traits other than the case-control status. Exploring secondary phenotypes can yield valuable insights into biological pathways and identify genetic variants influencing phenotypes of direct interest. All publications on secondary phenotypes have used standard statistical methods, such as least-squares regression for quantitative traits. Because of unequal selection probabilities between cases and controls, the case-control sample is not a random sample from the general population. As a result, standard statistical analysis of secondary phenotype data can be extremely misleading. Although one may avoid the sampling bias by analyzing cases and controls separately or by including the case-control status as a covariate in the model, the associations between a secondary phenotype and a genetic variant in the case and control groups can be quite different from the association in the general population. In this article, we present novel statistical methods that properly reflect the case-control sampling in the analysis of secondary phenotype data. The new methods provide unbiased estimation of genetic effects and accurate control of false-positive rates while maximizing statistical power. We demonstrate the pitfalls of the standard methods and the advantages of the new methods both analytically and numerically. The relevant software is available at our website.
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与人类血液低密度脂蛋白胆固醇、高密度脂蛋白胆固醇或甘油三酯相关的六个新位点。
影响因子：
30.8
作者：
Kathiresan, Sekar;Melander, Olle;Guiducci, Candace;Surti, Aarti;Burtt, Noel P.;Rieder, Mark J.;Cooper, Gregory M.;Roos, Charlotta;Voight, Benjamin F.;Havulinna, Aki S.;Wahlstrand, Bjorn;Hedner, Thomas;Corella, Dolores;Tai, E. Shyong;Ordovas, Jose M.;Berglund, Goran;Vartiainen, Erkki;Jousilahti, Pekka;Hedblad, Bo;Taskinen, Marja-Riitta;Newton-Cheh, Christopher;Salomaa, Veikko;Peltonen, Leena;Groop, Leif;Altshuler, David M.;Orho-Melander, Marju
通讯作者：
Orho-Melander, Marju
影响因子：
30.8
作者：
Willer, Cristen J.;Sanna, Serena;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
30.8
作者：
Loos, Ruth J. F.;Lindgren, Cecilia M.;Li, Shengxu;Wheeler, Eleanor;Zhao, Jing Hua;Prokopenko, Inga;Inouye, Michael;Freathy, Rachel M.;Attwood, Antony P.;Beckmann, Jacques S.;Berndt, Sonja I.;Bergmann, Sven;Bennett, Amanda J.;Bingham, Sheila A.;Bochud, Murielle;Brown, Morris;Cauchi, Stephane;Connell, John M.;Cooper, Cyrus;Smith, George Davey;Day, Ian;Dina, Christian;De, Subhajyoti;Dermitzakis, Emmanouil T.;Doney, Alex S. F.;Elliott, Katherine S.;Elliott, Paul;Evans, David M.;Farooqi, I. Sadaf;Froguel, Philippe;Ghori, Jilur;Groves, Christopher J.;Gwilliam, Rhian;Hadley, David;Hall, Alistair S.;Hattersley, Andrew T.;Hebebrand, Johannes;Heid, Iris M.;Herrera, Blanca;Hinney, Anke;Hunt, Sarah E.;Jarvelin, Marjo-Riitta;Johnson, Toby;Jolley, Jennifer D. M.;Karpe, Fredrik;Keniry, Andrew;Khaw, Kay-Tee;Luben, Robert N.;Mangino, Massimo;Marchini, Jonathan;McArdle, Wendy L.;McGinnis, Ralph;Meyre, David;Munroe, Patricia B.;Morris, Andrew D.;Ness, Andrew R.;Neville, Matthew J.;Nica, Alexandra C.;Ong, Ken K.;O'Rahilly, Stephen;Owen, Katharine R.;Palmer, Colin N. A.;Papadakis, Konstantinos;Potter, Simon;Pouta, Anneli;Qi, Lu;Randall, Joshua C.;Rayner, Nigel W.;Ring, Susan M.;Sandhu, Manjinder S.;Scherag, Andre;Sims, Matthew A.;Song, Kijoung;Soranzo, Nicole;Speliotes, Elizabeth K.;Syddall, Holly E.;Teichmann, Sarah A.;Timpson, Nicholas J.;Tobias, Jonathan H.;Uda, Manuela;Vogel, Carla I. Ganz;Wallace, Chris;Waterworth, Dawn M.;Weedon, Michael N.;Willer, Cristen J.;Wraight, Vicki L.;Yuan, Xin;Zeggini, Eleftheria;Hirschhorn, Joel N.;Strachan, David P.;Ouwehand, Willem H.;Caulfield, Mark J.;Samani, Nilesh J.;Frayling, Timothy M.;Vollenweider, Peter;Waeber, Gerard;Mooser, Vincent;Deloukas, Panos;McCarthy, Mark I.;Wareham, Nicholas J.;Barroso, Ines
通讯作者：
Barroso, Ines
DOI：
10.1198/016214505000000808
发表时间：
2006-03-01
影响因子：
3.7
作者：
Lin, DY;Zeng, D
通讯作者：
Zeng, D