Causal effects of body composition on lifespan: Mendelian randomization analysis.

Abstract

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. 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. 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. 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.