Preprint proposes unified framework for Hardy-Weinberg equilibrium testing on the X chromosome

Testing for Hardy-Weinberg equilibrium (HWE) is a standard quality-control step in genetic association studies and population-genetic analyses, used to flag genotyping errors, population stratification, and other data artefacts. However, applying HWE tests to X-linked loci is complicated by the fact that males are hemizygous — carrying only one copy of the X chromosome — and by the possibility that minor allele frequencies differ between males and females (sex-differential minor allele frequency, or sdMAF).

A preprint posted to bioRxiv presents a general statistical framework for HWE inference on the X chromosome that explicitly models sex-specific genotype structures and allows for sdMAF. The authors note that existing tests make diverse and often implicit assumptions about whether allele frequencies are equal across sexes and whether to include male genotypes, leading to null hypotheses that are poorly characterised and difficult to compare across software implementations.

The proposed framework unifies these approaches, allowing researchers to specify their assumptions explicitly and obtain well-defined tests. The work is relevant to large-scale GWAS quality control pipelines, population-genetic studies of X-linked variation, and any analysis that must handle X-chromosome data rigorously. As a preprint, the findings have not yet been peer-reviewed.