In PLOS Genetics, Baylor College of Medicine researchers dig into the dearth of genome-wide associations involving variants on the X chromosome relative to autosomal chromosomes. "We proposed a hypothesis of a real biological phenomenon underlying X versus autosomal differences in the density of GWAS-detected SNPs, namely that [the] X chromosome has a lower density of functional polymorphisms compared to autosomes because of a stronger selection against X chromosomal mutations," the researchers write, reasoning that "X chromosomal variants are more exposed to natural selection due to hemizygosity in males and X chromosome inactivation in females." For their analysis, the authors considered everything from overall SNP densities on the X chromosome and the autosomes to the numbers of SNPs found within or between genes, bringing in summary statistic data from thousands of prior genome-wide association studies to show that GWAS hits are several times lower on the X chromosome despite a SNP density that resembles that of other chromosomes.
Functional SNPs May Be Found at Lower Density on X Chromosome
Mar 01, 2023