Abstract
ObjectiveObservational studies have demonstrated a close relationship between obesity and longevity. The aim of this Mendelian randomization (MR) study is to investigate whether genetic determinants of visceral adipose tissue (VAT) accumulation are causally associated with longevity.MethodsIn this two-sample MR study, we used summary data of genetic determinants (single-nucleotide polymorphisms; p < 5 × 10−8) of VAT accumulation based on genome-wide association studies (GWASs). Longevity was defined as an age beyond the 90th or 99th survival percentile. The causal association of VAT accumulation with longevity was estimated with the inverse variance-weighted (IVW) method. Sensitivity analyses, including weighted median, MR-Egger, and MR–pleiotropy residual sum and outlier (PRESSO), were also employed to assess the stability of the IVW results.ResultsOur MR analysis used 221 genetic variants as instrumental variables to explore the causal association between VAT accumulation and longevity. In the standard IVW methods, VAT accumulation (per 1-kg increase) was found to be significantly associated with lower odds of surviving to the 90th (odds ratio [OR] = 0.69; 95% confidence interval [CI] 0.55 to 0.86, p = 8.32 × 10−4) and 99th (OR = 0.67; 95% CI 0.49 to 0.91, p = 0.011) percentile ages. These findings remained stable in sensitivity analysis.ConclusionThis MR analysis identified a causal relationship between genetically determined VAT accumulation and longevity, suggesting that visceral adiposity may have a negative effect on longevity.
Highlights
Obesity is a common human health problem, defined as an abnormal or excessive amount of body fat [1, 2]
In the standard inverse variance-weighted (IVW) methods, visceral adipose tissue (VAT) accumulation was found to be significantly associated with lower odds of surviving to the 90th and 99th (OR = 0.67; 95% CI 0.49 to 0.91, p = 0.011) percentile ages
These findings remained stable in sensitivity analysis. This Mendelian randomization (MR) analysis identified a causal relationship between genetically determined VAT accumulation and longevity, suggesting that visceral adiposity may have a negative effect on longevity
Summary
Obesity is a common human health problem, defined as an abnormal or excessive amount of body fat [1, 2]. People who consume more calories than spent during their daily activities and exercise are more likely to become obese or overweight [3]. Obesity is influenced by genetic factors in addition to other environmental influences, including the community, stress, sleep quality, medications, pregnancy, and some diseases [4, 5]. Obesity and overweight are typically assessed using anthropometric indicators such as body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio (WHR). Obesity is clinically defined according to the measurement of body fat percentage, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). Previous studies showed that VAT is unique, pathogenic fat depots [6,7,8]
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