Analysis of multiple SNPs in a candidate gene or region.

Genetic Epidemiology
Juliet Chapman, John Whittaker

Abstract

We consider the analysis of multiple single nucleotide polymorphisms (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 Chapman et al. ([2003] Hum. Hered. 56:18-31), Fisher's method for combining P-values, the minimum P-value approach, a Fourier-transform-based approach recently suggested by Wang and Elston ([2007] Am. J. Human Genet. 80:353-360) and a Bayesian score statistic proposed for microarray data by Goeman et al. ([2005] J. R. Stat. Soc. B 68:477-493). Some relationships between these methods are pointed out, and simulation results given to show that the minimum P-value and the Goeman et al. ([2005] J. R. Stat. Soc. B...Continue Reading

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Citations

May 17, 2011·Human Genetics·Clive J PetryDavid B Dunger
Oct 25, 2012·European Journal of Human Genetics : EJHG·John FergusonJoshua Sampson
Feb 10, 2012·European Journal of Human Genetics : EJHG·Valentina MoskvinaMichael C O'Donovan
Sep 19, 2009·American Journal of Epidemiology·Timothy J JorgensenAnthony J Alberg
Jan 11, 2011·Bioinformatics·V M LourençoM Kirst
Jul 6, 2010·Biostatistics·Holger SchwenderKatja Ickstadt
Jul 30, 2010·Carcinogenesis·Judith A SchwartzbaumMargaret R Wrensch
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Sep 15, 2009·BMC Genetics·Renfang JiangYilin Dai
Aug 11, 2011·PLoS Genetics·Hailiang HuangDan E Arking
Jul 9, 2011·PloS One·Benjamin LehneThomas Schlitt
Aug 4, 2012·PloS One·Marina EvangelouFrank Dudbridge
Oct 31, 2015·Genetic Epidemiology·Zhao-Hua LuUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Apr 12, 2014·Genetic Epidemiology·Daniel D Kinnamon, Eden R Martin
Jun 17, 2010·Kidney International·Abee L Boyles
Nov 20, 2009·Genetic Epidemiology·Duncan C Thomas
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Jul 20, 2011·Genetic Epidemiology·Saonli Basu, Wei Pan
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Apr 19, 2011·NeuroImage·Derrek P HibarUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Feb 26, 2014·BMC Systems Biology·Yu QianMikkel Heide Schierup

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