Genetic Obesity Risk Increases Likelihood of Leading Causes of Death, Study Reports

Ana Pena, PhD avatar

by Ana Pena, PhD |

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People with a greater genetic risk for obesity are more likely to have one of the leading causes of death, which include heart disease, stroke, diabetes, chronic obstructive pulmonary disease (COPD), lung cancer, kidney failure, and liver disease, a study reports.

Importantly, the impact of this genetic risk on type 2 diabetes, kidney failure and COPD is different in men and women. This has potential implications for public health strategies and indicates that sex-specific preventive measures may be needed, the researchers said.

Their study, “Causal relationships between obesity and the leading causes of death in women and men,” was published in the journal PLOS Genetics.

The prevalence of obesity is rising globally and has been linked to major cardiometabolic diseases, such as diabetes and heart disease. However, it remains unclear if obesity also plays a role in other leading causes of death.

Also, despite the known differences in obesity traits between women and men, few studies have explored how the impact of sex on genetic obesity risk can influence the risk for major diseases.

Researchers at the University of Oxford address these gaps with Mendelian randomization, a method that uses genetic data to infer if risk factors cause specific health outcomes.

First, they obtained sex-specific genetic risk scores for three obesity traits — body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI — based on more than 1,000 genetic variations known to be related to obesity.

Then, they used the UK Biobank, a large repository of biological samples and health data, to look for associations between genetic risk for obesity and major diseases in 228,466 women and 195,041 men.

In their analysis, the scientists accounted for factors that could influence risk of disease, including smoking, blood sugar levels, and blood pressure.

Results showed that having a higher genetic propensity for obesity traits increases the risk of several leading causes of death.

Specifically, people with a higher genetic risk for obesity were more likely to have coronary artery disease, the most common form of heart disease, stroke (particularly its most common form, ischemic stroke), COPD, lung cancer, diabetes, acute and chronic kidney failure, non-alcoholic fatty liver disease — caused by the accumulation of fat in the liver of people who drink little or no alcohol — and chronic liver disease.

Men and women showed different results. While higher BMI was linked to a greater risk of type 2 diabetes in women, a higher waist-hip ratio was associated with increased likelihood of COPD and chronic kidney disease in men.

“In summary, obesity traits are causally involved in the majority of the leading causes of death, and some obesity traits affect disease risk differently in men and women,” the researchers wrote.

“Our findings emphasize the importance of improved preventative measures and treatment of obesity-related disorders and implies that women and men may experience different disease sequelae from obesity, with potential implications for provision of health services and public health policy,” they added.

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