Centralizing the non-central chi-square: A new method to correct for population stratification in genetic case-control association studies

Genetic Epidemiology
Prakash GorroochurnDavid A Greenberg

Abstract

We present a new method, the delta-centralization (DC) method, to correct for population stratification (PS) in case-control association studies. DC works well even when there is a lot of confounding due to PS. The latter causes overdispersion in the usual chi-square statistics which then have non-central chi-square distributions. Other methods approach the noncentrality indirectly, but we deal with it directly, by estimating the non-centrality parameter tau itself. Specifically: (1) We define a quantity delta, a function of the relevant subpopulation parameters. We show that, for relatively large samples, delta exactly predicts the elevation of the false positive rate due to PS, when there is no true association between marker genotype and disease. (This quantity delta is quite different from Wright's F(ST) and can be large even when F(ST) is small.) (2) We show how to estimate delta, using a panel of unlinked "neutral" loci. (3) We then show that delta2 corresponds to tau the noncentrality parameter of the chi-square distribution. Thus, we can centralize the chi-square using our estimate of 6; this is the DC method. (4) We demonstrate, via computer simulations, that DC works well with as few as 25-30 unlinked markers, where t...Continue Reading

References

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Citations

Jul 19, 2013·Journal of Human Genetics·Min YuanHan Zhang
Nov 16, 2007·Biostatistics·Gang Zheng, Hon Keung Tony Ng
May 18, 2007·Annual Review of Genomics and Human Genetics·Robert C ElstonGang Zheng
Jul 23, 2011·Human Heredity·Prakash GorroochurnDavid A Greenberg
Dec 3, 2009·Human Genomics·Courtney Gray-McGuireRobert C Elston
Mar 21, 2007·PLoS Genetics·Paul D P PharoahUNKNOWN SEARCH Investigators
Dec 4, 2008·Genetic Epidemiology·Tony DaddCathryn M Lewis
Jun 5, 2008·International Journal of Andrology·Laura Rodriguez-Murillo, David A Greenberg
Aug 11, 2006·Statistics in Medicine·Robert C Elston, M Anne Spence
Feb 1, 2014·Evolution, Medicine, and Public Health·Michael D EdgeNoah A Rosenberg
Jun 19, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Prakash GorroochurnDavid A Greenberg
Oct 20, 2007·Nature Protocols·Krina T Zondervan, Lon R Cardon

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