title: How to include chromosome X in your genome-wide association study.
abstract: 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.
authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; DZHK (German Centre for Cardiovascular Research), Lübeck, Germany.
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Christina
authors.initials: C
authors.lastname: Loley
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
mesh_terms: D000465:Algorithms; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male
keywords: case-control association; sex chromosomes