Population genomic analysis uncovers sex- and ancestry-specific Hardy-Weinberg disequilibrium in diverse genomes, indicating technical sequencing artifacts drive most deviations.
Key Points
To assess genome-wide, sex-stratified deviations from Hardy-Weinberg equilibrium across diverse ancestral populations using telomere-to-telomere-aligned high-coverage whole genome sequencing.
Analyzed high-coverage whole genome sequencing from 2,490 individuals across five super-populations in the 1000 Genomes Project aligned to T2Tv2.
Restricted evaluation to bi-allelic SNPs with non-missing genotypes and minor allele frequency ≥5% in both sexes across all five super-populations.
Quantified Hardy-Weinberg disequilibrium (HWD) via an allele-based framework, conducted second-order omnibus meta-analyses across populations and sexes, and built a multivariate predictor based on sequence features.
At genome-wide significance (p < 5e-8), 0.9% of autosomal SNPs showed significant HWE deviations, predominantly associated with genomic features indicative of poor sequence quality.
Restricting analyses to reliable genomic regions reduced deviations to 255 autosomal SNPs and one non-pseudoautosomal chromosome X SNP, with 140 autosomal SNPs exhibiting significant heterogeneity across populations but not sexes.
Identified eight SNPs within a 15-bp region on chromosome 14q31.3 displaying excess heterozygosity across both sexes specifically within the African super-population.