Causal effects of body composition on lifespan: Mendelian randomization analysis

Abstract

Background: Observational studies examining the relation of body composition with lifespan are inconsistent. We conducted a Mendelian Randomization (MR) study to assess effects of key features of body composition on lifespan. Methods: We conducted a MR study using inverse variance weighting to investigate the impact of measures of body composition on lifespan, and we also adjusted fat-free mass and appendicular lean mass for potential confounding by fat mass, and assessed mediation by waist circumference in men and women. Results: In univariable MR, genetically predicted fat mass (per standard deviation higher) decreased men’s lifespan by 2.69 years (95% confidence interval [CI] –3.14 to –2.23) and women’s by 2.48 years (95% CI –3.04 to –1.93), with similar findings for body fat percentage and waist circumference. Appendicular lean mass and grip strength were positively associated with lifespan in men, but not women. In multivariable MR, fat-free mass was also beneficial for men. The effect of BMI on lifespan was largely mediated by waist circumference. Conclusion: Our study provides additional evidence highlighting the role of body composition rather than relying solely on BMI, with possibly a greater role of lean or fat-free mass in men. Waist circumference is a key target of intervention for men and women.