Analysis of multiple SNPs in a candidate gene or region.
Analysis of multiple SNPs in a candidate gene or region.
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DOI：
10.1002/gepi.20330
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发表时间：
2008-09
影响因子：
2.1
通讯作者：
Whittaker, John
中科院分区：
文献类型：
--
作者：
Chapman, Juliet;Whittaker, John
我们考虑对一个基因或区域内的多个 SNP 进行分析。此类数据最简单的分析是基于一系列单一 SNP 假设检验，然后对多重检验进行校正，但直观上合理的是，SNP 的联合分析将具有更高的功效，特别是当可能尚未观察到因果基因座时。然而，标准检验，例如基于不受限制的替代假设的似然比检验，往往具有大量自由度，因此功效较低。这激发了许多替代测试统计数据。在这里，我们比较了几种竞争方法，包括多变量评分检验（霍特林检验）、Fisher 组合 p 值的方法、最小 p 值方法、最近建议的基于傅里叶变换的方法以及针对微阵列数据提出的贝叶斯评分统计。指出了这些方法之间的一些关系，并给出了模拟结果，表明最小 p 值和这些方法在一系列场景下都能很好地工作。 Wang 和 Elston 的方法常常表现不佳。我们解释了原因，并展示了如何大幅提高其性能。
We consider the analysis of multiple SNPs within a gene or region. The simplest analysis of such data is based on a series of single SNP hypothesis tests, followed by correction for multiple testing, but it is intuitively plausible that a joint analysis of the SNPs will have higher power, particularly when the causal locus may not have been observed. However, standard tests, such as a likelihood ratio test based on an unrestricted alternative hypothesis, tend to have large numbers of degrees of freedom and hence low power. This has motivated a number of alternative test statistics. Here we compare several of the competing methods, including the multivariate score test (Hotelling’s test) of, Fisher’s method for combining p-values, the minimum p-value approach, a Fourier transform based approach recently suggested by and a Bayesian score statistic proposed for microarray data by. Some relationships between these methods are pointed out, and simulation results given to show that the minimum p-value and the approaches work well over a range of scenarios. The Wang and Elston approach often performs poorly; we explain why, and show how its performance can be substantially improved.
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影响因子：
9.8
作者：
Morris, AP;Whittaker, JC;Balding, DJ
通讯作者：
Balding, DJ
影响因子：
1.8
作者：
Chapman, JM;Cooper, JD;Clayton, DG
通讯作者：
Clayton, DG
影响因子：
9.8
作者：
Fan, RZ;Knapp, M
通讯作者：
Knapp, M
影响因子：
64.8
作者：
Burton, Paul R.;Clayton, David G.;Cardon, Lon R.;Craddock, Nick;Deloukas, Panos;Duncanson, Audrey;Kwiatkowski, Dominic P.;McCarthy, Mark I.;Ouwehand, Willem H.;Samani, Nilesh J.;Todd, John A.;Donnelly, Peter;Barrett, Jeffrey C.;Davison, Dan;Easton, Doug;Evans, David;Leung, Hin-Tak;Marchini, Jonathan L.;Morris, Andrew P.;Spencer, Chris C. A.;Tobin, Martin D.;Attwood, Antony P.;Boorman, James P.;Cant, Barbara;Everson, Ursula;Hussey, Judith M.;Jolley, Jennifer D.;Knight, Alexandra S.;Koch, Kerstin;Meech, Elizabeth;Nutland, Sarah;Prowse, Christopher V.;Stevens, Helen E.;Taylor, Niall C.;Walters, Graham R.;Walker, Neil M.;Watkins, Nicholas A.;Winzer, Thilo;Jones, Richard W.;McArdle, Wendy L.;Ring, Susan M.;Strachan, David P.;Pembrey, Marcus;Breen, Gerome;St Clair, David;Caesar, Sian;Gordon-Smith, Katherine;Jones, Lisa;Fraser, Christine;Green, Elain K.;Grozeva, Detelina;Hamshere, Marian L.;Holmans, Peter A.;Jones, Ian R.;Kirov, George;Moskvina, Valentina;Nikolov, Ivan;O'Donovan, Michael C.;Owen, Michael J.;Collier, David A.;Elkin, Amanda;Farmer, Anne;Williamson, Richard;McGuffin, Peter;Young, Allan H.;Ferrier, I. Nicol;Ball, Stephen G.;Balmforth, Anthony J.;Barrett, Jennifer H.;Bishop, D. Timothy;Iles, Mark M.;Maqbool, Azhar;Yudasheve, Nadira;Hall, Alistair S.;Braund, Peter S.;Dixon, Richard J.;Mangino, Massimo;Stevens, Suzanne;Thompson, John R.;Bredin, Francesca;Tremelling, Mark;Parkes, Miles;Drummond, Hazel;Lees, Charles W.;Nimmo, Elaine R.;Satsangi, Jack;Fisher, Sheila A.;Forbes, Alistair;Lewis, Cathryn M.;Onnie, Clive M.;Prescott, Natalie J.;Sanderson, Jeremy;Mathew, Christopher G.;Barbour, Jamie;Mohiuddin, M. Khalid;Todhunter, Catherine E.;Mansfield, John C.;Ahmad, Tariq;Cummings, Fraser R.;Jewell, Derek P.;Webster, John;Brown, Morris J.;Lathrop, G. Mark;Connell, John;Dominiczak, Anna;Marcano, Carolina A. Braga;Burke, Beverley;Dobson, Richard;Gungadoo, Johannie;Lee, Kate L.;Munroe, Patricia B.;Newhouse, Stephen J.;Onipinla, Abiodun;Wallace, Chris;Xue, Mingzhan;Caulfield, Mark;Farrall, Martin;Barton, Anne;Bruce, Ian N.;Donovan, Hannah;Eyre, Steve;Gilbert, Paul D.;Hider, Samantha L.;Hinks, Anne M.;John, Sally L.;Potter, Catherine;Silman, Alan J.;Symmons, Deborah P. M.;Thomson, Wendy;Worthington, Jane;Dunger, David B.;Widmer, Barry;Frayling, Timothy M.;Freathy, Rachel M.;Lango, Hana;Perry, John R. B.;Shields, Beverley M.;Weedon, Michael N.;Hattersley, Andrew T.;Hitman, Graham A.;Walker, Mark;Elliott, Kate S.;Groves, Christopher J.;Lindgren, Cecilia M.;Rayner, Nigel W.;Timpson, Nicholas J.;Zeggini, Eleftheria;Newport, Melanie;Sirugo, Giorgio;Lynons, Emily;Vannberg, Fredrik;Brown, Matthew A.;Franklyn, Jayne A.;Heward, Joanne M.;Simmonds, Matthew J.;Hill, Adrian V. S.;Bradbury, Linda A.;Farrar, Claire;Pointon, Jennifer J.;Wordsmith, Paul;Gough, Stephen C. L.;Seal, Sheila;Stratton, Michael R.;Rahman, Nazneen;Ban, Maria;Goris, An;Sawcer, Stephen J.;Compston, Alistair;Conway, David;Jallow, Muminatou;Bumpstead, Suzannah J.;Chaney, Amy;Downes, Kate;Ghori, Mohammed J. R.;Gwilliam, Rhian;Inouye, Michael;Keniry, Andrew;King, Emma;McGinnis, Ralph;Potter, Simon;Ravindrarajah, Rathi;Whittaker, Pamela;Withers, David;Easton, Doug;Pereira-Gale, Joanne;Hallgrimsdottir, Ingilef B.;Howie, Bryan N.;Su, Zhan;Teo, Yik Ying;Vukcevic, Damjan;Bentley, David;Caulfield, Mark;Mathew, Christopher G.;Worthington, Jane
通讯作者：
Worthington, Jane
影响因子：
4.5
作者：
Tachmazidou, Ioanna;Verzilli, Claudio J.;De Iorio, Maria
通讯作者：
De Iorio, Maria