Genetically predicted glucosamine and longevity: A Mendelian randomization study

Abstract

Background & aims: Glucosamine is known to affect different health outcomes, however its effect on male and female lifespan is still unclear. We conducted a two-sample Mendelian randomization (MR) study to investigate the association of genetically proxied glucosamine with longevity.

Methods: Using genetic data from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) consortium for 461,384 individuals, we identified five genetic variants as instrumental variables for genetically predicted glucosamine. We obtained genetic associations of these variants with parental longevity as combined parental age at death (n = 208,118), mother's age at death (n = 246,941) and father's age at death (n = 317,652). We used the inverse-variance weighted method to estimate the effect of a 1-standard deviation (SD) increase in genetically predicted glucosamine on parental longevity.

Results: We found a positive effect of genetically predicted higher glucosamine status on life expectancy using combined parental age at death. A 1-SD increase in genetically predicted glucosamine was associated with higher odds of combined parental age at death (odds ratio, 2.64; 95% CI 1.26, 5.54; P = 0.01), and maternal age at death (odds ratio, 1.73; 95 CI 1.04, 2.89; P = 0.03), but not paternal age at death (odds ratio, 1.32; 95% CI 0.81, 2.15; P = 0.27). Based on follow-up sensitivity analyses, we did not find evidence of pleiotropic effects of the genetic variants.

Conclusions: Lifelong higher levels of glucosamine may increase life expectancy. Positive effects of glucosamine were associated with maternal age at death only. The clinical implications of this sex-specific finding warrant further investigation.

Keywords: Glucosamine; Lifespan; Longevity; Maternal; Mendelian randomization; Paternal.