Testing association for markers on the X chromosome

Genet Epidemiol. 2007 Dec;31(8):834-43. doi: 10.1002/gepi.20244.


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.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Chromosomes, Human, X*
  • Female
  • Genetic Diseases, X-Linked*
  • Genetic Linkage
  • Genetic Markers*
  • Humans
  • Macular Degeneration / genetics
  • Male
  • Polymorphism, Single Nucleotide
  • Primary Ovarian Insufficiency / genetics
  • Statistics as Topic*


  • Genetic Markers