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Cardiovascular Diabetology

Genetic analysis questions obesity’s apparent survival benefit

In UK Biobank, a higher genetic score tracked higher death risk: the hazard ratio, a relative risk measure, was 1.05 per standard-deviation increase.

Paper by Jian Lu, Shuaigang Sun, Shunwei Wang, 3 more authorsWenge Li · China-Japan Friendship Hospital
Figure 1 from Cardiovascular Diabetology
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Figure 1. Lu et al., CC BY-NC-ND
Genetic association study of 488,656 UK Biobank participantsPopulations

Mendelian randomization, dose-response

Limit: BMI is only a proxy for adiposity, limiting interpretation of its mortality associations

Edited by Boris Djordjevic · AgingResearch.News

Paper
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An observational analysis examined 488,656 UK Biobank participants and 13,114 National Health and Nutrition Examination Survey participants. Researchers compared body mass index, a measure based on weight and height, with mortality across stages of cardiovascular-kidney-metabolic syndrome, which links heart, kidney and metabolic disease.

In both cohorts, mortality followed a broadly U-shaped pattern. The lowest point generally shifted toward higher body mass index as disease stage advanced. In UK Biobank, however, a genetic score indicating susceptibility to higher body mass index showed an approximately linear association with higher mortality, without a survival advantage. A standard deviation measures how widely scores vary. The authors suggested that the apparent obesity paradox may partly reflect body mass index’s limitations as a measure of body fat, rather than a true protective effect of excess fat.

Why it matters

For assessing risk from age-related cardiovascular disease, the authors supported using measures of body fat beyond body mass index.

Caveats

Observational associations can be distorted by other health differences and by illness affecting weight. Genetic susceptibility is not the same as testing whether a weight-change intervention alters survival.

From the paper

Result

Conversely, BMI-GRS showed approximately linear adverse associations with all-cause mortality (HR per 1-SD increment 1.05, 95% CI 1.04–1.06) and CVD mortality (HR 1.10, 95% CI 1.07–1.12), and mortality risk increased progressively with advancing CKM stage across BMI-GRS strata (P for trend < 0.001).

Results

Quoted word for word from the full text on link.springer.com.

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