Genetic Risk for Obesity Linked to Shorter Lifespan, Study Reports

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Having a greater genetic likelihood for high blood pressure and obesity may correlate with a shorter lifespan, a large international study reports.

This type of analysis could help identify those most likely to benefit from medical or lifestyle interventions, according to the scientists.

The study, “Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan,” was published in the journal Nature Medicine.

Human biology is dictated by both genetic and non-genetic factors (environment, lifestyle, etc.), which play a major role in determining a person’s risk of a variety of diseases. Figuring out which factors predispose individuals toward worse health outcomes is important, because preventive treatments can then be targeted to people at highest risk.

Researchers examined whether the genetic risk for traits such as height, weight, and blood pressure is associated with lifespan.

For this purpose, they calculated polygenic risk scores (PRS), or the genetic susceptibility to developing each trait. This kind of analysis is useful because “genetic susceptibility is less affected by acquired confounding factors,” the researchers wrote.

The scientists analyzed three nationwide databases: one from Japan, one from Finland, and one from the United Kingdom. In total, these databases included information on 675,898 people.

Building on previously reported results, the study showed that the PRS for high systolic blood pressure was significantly associated with a shorter lifespan as well as shorter parental lifespan. This genetic risk was linked to death from cardiovascular disease and cerebrovascular disease (e.g., stroke). The correlation of high blood pressure with shorter lifespan was mostly driven by individuals with metabolic conditions, such as type 2 diabetes.

“These results recapitulated epidemiological knowledge that hypertension is one of the strongest risk factors of mortality among patients with cardiovascular, cerebrovascular, and metabolic diseases,” the researchers wrote.

Additional analyses suggested that the effect of high blood pressure PRS on lifespan was more pronounced in males than in females, which is consistent with previous research.

Genetic risk for body mass index (BMI), a ratio of weight to height, was also significantly associated with lifespan.

In the United Kingdom and Finland data sets, having high genetic scores for greater BMI was associated with a 6%–7% higher risk of shorter lifespan. The effect was much smaller in the Japanese database. According to the researchers, this could be due to an overall lower rate of obesity in Japan, which warrants further studies.

Among the U.K. data set, the genetic risk for high BMI was significantly associated with death from cerebrovascular disease. The association between this risk and lifespan was driven primarily by people with unstable angina (chest pain).

“These analyses pinpointed the target individuals who would benefit most from the modification of obesity,” the researchers wrote. “Although the magnitude of effect sizes in the association of PRSs with lifespan was relatively small, the magnitude of effect sizes in which the trait itself [such as obesity] affects lifespan … would be expected to be larger in terms of population health.”

Additional analyses showed that both blood pressure and BMI risk scores were not significantly affected by lifestyle traits. For example, quitting smoking was equally beneficial for people with the highest and the lowest blood pressure risk score.

“This suggests that even people with a high genetic burden of hypertension or obesity could benefit from lifestyle modifications such as smoking cessation and regular exercise,” the team wrote.

These findings suggest that BMI and blood pressure affect lifespan on a global scale. They also identify who may benefit most from interventions aimed at lowering weight and/or blood pressure.

More broadly, this study is a proof-of-concept for the kind of research that can be done using large data sets from across the world.

“With global biobanks’ efforts … we have shown a potential application of genetics to improve population health by providing information on modifiable risk factors driving our health outcomes,” the researchers concluded.

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