Genetics May Influence Disease Prevalence By Gender

Article

Genetics that determine physical traits may play a large role in prevalence of conditions such as multiple sclerosis, autism, and diabetes.

New findings suggest that genetics may influence the reason more men or women develop certain diseases, including multiple sclerosis (MS), autism, type 1 diabetes.

It is well known that more women than men develop MS, while more men than women develop autism. Other diseases, such as heart disease, can present differently among the sexes, and patients are known to respond differently to treatments based on their gender. This has raised questions about how genetics influence the prevalence of diseases among the sexes.

However, despite the importance of genetic differences between the sexes, there is still little understanding of how biology drives the differences.

"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," said senior study author Lauren A. Weiss, PhD.

In 2 new studies, a team of investigators examined data from a genome-wide association study (GWAS) to determine any patterns that may support or disprove their hypothesis of gender differences in MS development.

GWAS is an approach that involves scanning markers across DNA to discover genetic variations in patients with a certain disease. Discovering a genetic variant that is linked to a characteristic typically implies that a nearby gene is involved.

In a new study published by PLoS Genetics, the authors examined why autism is more prevalent among boys compared with girls. The investigators analyzed several hypotheses, such as diagnosis, autism presenting an “extreme male brain” more common among males, or the condition being driven by sex hormones.

However, they did not discover any of those factors to be involved. Instead, the authors discovered that the risk for developing autism may be linked to genetic variants linked to height, weight, body mass index, and waist-to-hip ratio in men and women. These findings indicate that sex could influence autism risk, according to the study.

“The results indicate that there are fundamental genetic sex differences in autism,” Dr Weiss said. “It suggests that genetic variants that may be important predictors of autism risk for girls may not be so important for boys, or vice versa. This means that interpretation of genetic testing in autism could potentially be improved and refined by considering sex. Further in the future, similar implications should be considered for autism treatments — if there are sex differences in the underlying biology, response to specific treatments might also be different by sex.”

In a follow-up study published by Genetics, the team of investigators explored the role of sex differences in 9 other diseases. They studied ankylosing spondylitis and type 1 diabetes, which are more common among men, multiple sclerosis and rheumatoid arthritis, which are more common among women, and those that occur similarly between the sexes, such as bipolar disorder, coronary artery disease, Crohn’s disease, hypertension, and type 2 diabetes.

The team analyzed data that would determine the reasoning behind sex differences in these specific diseases. They discovered that sex played a key role in the risk associated with these diseases, even those previously believed to occur with the same frequency.

Numerous diseases seemed to be influenced by genes regulated by androgens or estrogens, and the same differences that influence genetic traits contributed to the risk of developing 5 of these diseases, according to the study.

“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,” Dr 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.”

Interestingly, the authors discovered an interaction with sex for genetic risk factors for multiple sclerosis and the heritability of hypertension more common among women, according to the study. Since hypertension occurs at the same frequency, the investigators believe that environmental factors may play a larger role in male hypertension than previously believed.

While these findings still need to be confirmed in further studies, the process that leads to development of MS may differ between men and women, and could lead to new research and treatments for certain diseases, the study concluded.

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