How to include chromosome X in your genome-wide association study

Genet Epidemiol. 2014 Feb;38(2):97-103. doi: 10.1002/gepi.21782. Epub 2014 Jan 9.


In current genome-wide association studies (GWAS), the analysis is usually focused on autosomal variants only, and the sex chromosomes are often neglected. Recently, a number of technical hurdles have been described that add to a reluctance of including chromosome X in a GWAS, including complications in genotype calling, imputation, and selection of test statistics. To overcome this, we provide a "how to" guide for analyzing X chromosomal data within a standard GWAS. Following a general pipeline for GWAS, we highlight the steps in which the X chromosome requires specific attention, and we give tentative advice for each of these. Through this, we show that by selection of sensible algorithms and parameter settings, the inclusion of chromosome X in GWAS is manageable. Closing this gap is expected to further elucidate the genetic background of complex diseases, especially of those with sex-specific features.

Keywords: case-control association; sex chromosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Chromosomes, Human, X / genetics*
  • Female
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Male