Genes That Influence Physical Traits May Be Reason MS More Common in Women

The key to why more women than men develop multiple sclerosis (MS) may be genes that influence physical traits, such as weight, height, and body shape, according to a new study.

Researchers caution that the findings need to be verified, but they said processes leading to disease may differ between the sexes — a crucial insight with implications for researching and treating MS.

The team from the University of California, San Francisco published the study, “Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits,” in the journal Genetics.

Researchers analyzed data from a genome-wide association study (GWAS) to search for patterns that might support or rule out hypotheses about the origins of sex differences in a number of diseases. They then compared those patterns with physical traits that differ between the sexes, such as height, body mass index (BMI), and waist-to-hip ratios. (GWAS is an approach that involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Identifying a gene variant that is linked to a characteristic often indicates nearby genes may be involved.)

“While some studies have looked at small regions of the genome or tried to support one specific hypothesis with respect to sex differences, few studies have looked at the question from a comprehensive genome-wide perspective,” Lauren A. Weiss, PhD, associate professor of psychiatry at UCSF and the study’s senior author, said in a press release.

The team also explored whether sex differences in disease risk could be explained by different levels of testosterone or estrogen, or differences in the sex chromosomes — the fact that women have two X chromosomes and men have an X and a Y.

In MS and a number of other conditions, the researchers found, common genetic factors that influence physical traits do impact the risk of developing disease.

The work was a direct follow-up of research investigating the same questions in patients with autism — a disease that more often occurs in men. That study, which was published in the journal PLOS Genetics late last year, indicated that genes behind male and female body composition differences influence autism risk.

“We don’t know yet why this occurs, but it does imply that the same biological pathways that influence physical sex differences also impact a number of common diseases and disorders,” Weiss said.

“Many people are excited about the idea of precision medicine, or how medical care can be optimized for an individual. Well, sex is something that we already know about every individual. A better understanding of how sex impacts genetic risk for disease could be a great start to improving our understanding, diagnosis, and treatment or prevention of common diseases.” Weiss concluded.