Major sex differences in allele frequencies for X chromosome variants in the 1000 Genomes Project data

Abstract

AbstractAn unexpectedly high proportion of SNPs on the X chromosome in the 1000 Genomes Project phase 3 data were identified with significant sex differences in minor allele frequencies (sdMAF). sdMAF persisted for many of these SNPs in the recently released high coverage whole genome sequence, and it was consistent between the five super-populations. Among the 245,825 common biallelic SNPs in phase 3 data presumed to be high quality, 2,039 have genome-wide significant sdMAF (p-value <5e-8). sdMAF varied by location: (NPR)=0.83%, pseudo-autosomal region (PAR1)=0.29%, PAR2=13.1%, and PAR3=0.85% of SNPs had sdMAF, and they were clustered at the NPR-PAR boundaries, among others. sdMAF at the NPR-PAR boundaries are biologically expected due to sex-linkage, but have generally been ignored in association studies. For comparison, similar analyses found only 6, 1 and 0 SNPs with significant sdMAF on chromosomes 1, 7 and 22, respectively. Future X chromosome analyses need to take sdMAF into account.