Sex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity

► Genetic/epigenetic interaction influences disease severity in lupus patients. ► Higher genetic risk score to DNA methylation ratio correlated with increased severity of lupus flares. ► Men with lupus require a higher genetic risk to DNA methylation ratio to achieve a lupus flare of equal severity to women. ► Understanding the mechanisms behind genetic/epigenetic interaction might help to explain the missing heritability and sex disparity in lupus.