Testing association for markers on the X chromosome

Test statistics for association between markers on autosomal chromosomes and a disease have been extensively studied. No research has been reported on performance of such test statistics for association on the X chromosome. With 100,000 or more single‐nucleotide polymorphisms (SNPs) available for genome‐wide association studies, thousands of them come from the X chromosome. The X chromosome contains rich information about population history and linkage disequilibrium. To identify X‐linked marker susceptibility to a disease, it is important to study properties of various statistics that can be used to test for association on the X chromosome. In this article, we compare performance of several approaches for testing association on the X chromosome, and examine how departure from Hardy‐Weinberg equilibrium would affect type I error and power of these association tests using X‐linked SNPs. The results are applied to the X chromosome of Klein et al. [2005], a genome‐wide association study with 100K SNPs for age‐related macular degeneration. We found that a SNP (rs10521496) covered by DIAPH2 , known to cause premature ovarian failure (POF) in females, is associated with age‐related macular degeneration. Genet. Epidemiol . 2007. Published 2007 Wiley‐Liss, Inc.