Over 1,000 Sex-Specific Genetic Switches Explain Women’s Higher Autoimmune Risk

Using single-cell sequencing, scientists from the Garvan Institute of Medical Research and UNSW Sydney examined 1.25 million peripheral blood mononuclear cells from the OneK1K cohort, revealing more than 1,000 expression quantitative trait loci that function uniquely in either sex. Male samples showed higher monocyte proportions and gene activity focused on basic cellular maintenance, while female samples contained more B cells and regulatory T cells with heightened expression of inflammation-related genes.

This sex-biased genetic architecture helps explain why women are diagnosed with autoimmune conditions, such as lupus, at rates up to nine-to-one compared with men. The findings challenge the assumption that sex differences stem mainly from X and Y chromosomes, showing most switches reside on autosomes. Researchers argue that acknowledging these differences is essential for developing precision medicines that address the distinct immune baselines of men and women.