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Genetic Risk for High Blood Pressure, Obesity Also Linked to Shorter Lifespan

NEW YORK – People who have an increased genetic risk for conditions like high blood pressure or obesity are also more likely to have shorter lifespans, a new analysis of biobank data from three countries has found.

People's risk of disease is influenced both by environmental and genetic factors, and polygenic risk scores have increasingly been explored as a means of improving population health by determining who is at high risk for certain conditions and may benefit from prevention efforts. 

An Osaka University-led team of researchers analyzed genetic and clinical data on about 700,000 people from three biobanks to examine the relationship between genetic susceptibility to a number of common traits and lifespan. As they reported in Nature Medicine on Monday, the researchers found genetic susceptibility to high blood pressure and obesity were associated with shorter lifespans. They noted, though, that the link between obesity and lifespan was more pronounced among individuals with European ancestry.

"The genetic code contains a lot of information, most of it of unknown significance to us," senior author Yukinori Okada, a professor of statistical genetics at Osaka, said in a statement. "The goal of our study was to understand how we can utilize genetic information to discover risk factors for important health outcomes that we can directly influence as healthcare professionals."

Using data on 179,066 individuals from BioBank Japan and 361,194 individuals from the UK Biobank, the Osaka team conducted an observational study to identify clinical biomarkers associated with lifespan. The biobanks had amassed data on participants including measures of blood pressure, cholesterol, liver function, and more. 

They generated polygenic risk scores for these traits, which they first tested in the BioBank Japan cohort and replicated in the UK Biobank cohort and in 135,638 people from the FinnGen biobank.

High polygenic risk scores for blood pressure-related traits — such as systolic blood pressure, diastolic blood pressure, and mean arterial pressure — were significantly associated with shorter lifespans. Individuals with the highest systolic blood pressure had 1.46-fold higher risk of hypertension and increased mortality. This association held across ethnicities.

However, a high polygenic risk score for body-mass index and obesity were more strongly associated with shorter lifespan in the UK Biobank and FinnGen cohorts than in the BioBank Japan cohort. This suggested the Japanese cohort might somehow be protected from that effect of obesity on lifespan, though the researchers noted that the Japanese cohort was a hospital-based one, not healthy volunteers like the UK Biobank.

In the UK Biobank cohort, a high polygenic risk score for BMI was strongly linked to cerebrovascular death and its effect was particularly acute on those with unstable angina. 

A trans-ethnic meta-analysis implicated high cholesterol levels in shortened lifespans. It also found that the effect of the diastolic blood pressure polygenic risk score on lifespan was higher in men than in women.

Additionally, a trans-ethnic Mendelian randomization study uncovered causal relationships between lifespan and systolic blood pressure and mean arterial blood pressure in the BioBank Japan cohort, and between lifespan and BMI and body weight in the UK Biobank and FinnGen cohorts.

These findings, the researchers noted, suggest that people with high genetic risk of hypertension or obesity might benefit from making lifestyle changes such as quitting smoking and getting regular exercise. "These are striking results that show how genetics can be used to predict health risks," Okada added. "Our findings could offer an approach to utilize genetic information to seek out health risk factors with the goal of providing targeted lifestyle changes and medical treatment. Ultimately, these approaches would be expected to improve the health of the overall population."