Genetics Contribute to Hypertension, UAB Revealed

Men are more likely than women to suffer from hypertension or high blood pressure. The reasons for this disparity are not well understood. In a recent study published in Circulation: Genomic and Precision Medicine, researchers at the University of Alabama at Birmingham Marnix E. Heersink School of Medicine reviewed nationwide data encompassing more than 200,000 individuals from diverse racial and ethnic backgrounds to assess the role of genetics in sex differences in hypertension.

Hypertension affects roughly half of the population in the United States. It is the most significant risk factor for the onset of cardiovascular disorders such as coronary heart disease, heart failure, and stroke. Hypertension management accounts for over $200 billion in annual health-care spending. According to the researchers, forecasting the development of hypertension may aid in the development of preventive techniques to lower the risk of heart disease.

The current study used data from the U.K. Biobank, which contained more than 486,000 people of various ancestry groups, to conduct genomewide association studies for systolic blood pressure. A genomewide association study, or GWAS, is an analytical tool that aids in the identification of risk variables that influence SBP.

“The GWASs were conducted for each sex individually, which allowed the team to account for the varying effects of genetic variants on SBP by sex,” explained Naman Shetty, M.D., a research fellow in the UAB Division of Cardiovascular Disease and the study’s first author. “The GWAS variants were combined to create sex-specific polygenic risk scores, also known as PRS, for systolic blood pressure.” The PRS reveals a hereditary propensity to hypertension.”

Shetty and his colleagues next applied the sex-specific PRS to the All of Us cohort, an NIH-funded research program that recruits people from all walks of life from throughout the country to promote precision medicine. The researchers conducted a sex-specific investigation of the PRS’s connection with hypertension in about 200,000 people.

“We found that the PRS was more profoundly associated with hypertension in females compared to males,” Shetty went on to say. “Females with a high PRS had a higher risk of hypertension compared with males with a high PRS, and females with a low PRS had a lower risk of hypertension than males with a low PRS.”

Furthermore, Shetty says the study revealed that the association between genetic risk and hypertension varied before and after menopause. Pre-menopausal women with a high genetic risk had a higher risk of hypertension than men, but the risk became equivalent after menopause.

“This comprehensive study highlights the role of genetics in sex differences in hypertension,” said Pankaj Arora, M.D., senior author of the study and associate professor in the UAB Division of Cardiovascular Disease.

According to Arora, further research should concentrate on the genetic variations that were solely connected with SBP in each sex. The study of the activities of these genetic variations will help researchers better understand sex-specific mechanisms of SBP regulation and the likelihood of sex-specific responses to drugs.

“For years, we have been aware of gender disparities in cardiovascular disease,” said Arora, a cardiologist at the UAB Cardiovascular Institute. “Studies like these point to a biological basis for understanding these differences.” Such efforts will aid in the development of precision medicine approaches to treating hypertension in order to eliminate gender inequities in cardiovascular disease burden.”

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