Let’s Talk About Sex… in GWAS

By Bethann Hromatka

The saying “men are from Mars, women are from Venus,” may have originated from personality differences between the sexes, but it also rings true for complex diseases that affect one sex more than the other. For instance, the prevalence of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes is higher in women than men. In addition, some diseases progress faster in one sex, and men and women can have different responses to certain therapies.

A recent study by Linda Liu and colleagues at Stanford University attempted to identify some of the genetics underlying these differences. They analyzed data from one of the first genome-wide association studies (GWAS)—carried out by the Wellcome Trust Case Control Consortium (WTCCC), which looked at seven common diseases—in order to find gene variants that influence disease risk in only one sex. Most studies look for genetic variants associated with disease without performing in-depth analyses to identify sex-specific effects.

Although this is standard practice in GWAS, Liu and authors point out that some studies may have failed to find SNPs that influence disease risk in only one gender because they grouped men and women together. A combined sex GWAS is unlikely to detect a SNP that is simultaneously risky for women, but protective for men, because the effects will cancel each other out. Alternatively, if a SNP only influences risk in one sex, the association might not be observed unless the data from men and women are analyzed separately.

After applying novel statistical methods, the authors identified two female-specific SNPs linked to Crohn’s disease and a male-specific SNP associated with coronary artery disease. Although these associations were also found in the combined sex analysis by the WTCCC, the new findings provide evidence that the overall effects are driven by one sex and may not be applicable to both. Liu and her colleagues argue that GWAS should recruit larger cohorts and most importantly, equal numbers of women and men in order to systematically study sex-specific effects of genetic variants on disease.

This study suggests that most of the genetic associations identified to date are either those that impact the population as a whole, or those that are strong enough in one sex to produce an effect in a combined analysis. This implies that many more associations could be found that are specific to one sex. Says Liu and authors, “studying sex differences can help provide a missing link in terms of different gene-endocrine and gene-environment interactions in males and females.”

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.


  • Frank White

    Thanks for this. Theory predicts these results, but empirical evidence is needed to move people and stimulate funding.

    I seems reasonable that personal genome services like 23andMe would make analysis of the X chromosome more widely available not only to signal needs for monitoring potential chronic conditions but also to supplement genealogical research.

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