Genetic Associations of Birthweight, Childhood, and Adult BMI on Testosterone Levels: A Mendelian Randomization.

Abstract

Birthweight, childhood, and adult BMI have been indicated associated with the testosterone levels, but the current studies are plagued by significant heterogeneity, and a consensus about the role of these weight traits in testosterone levels is still debated. This work aims to evaluate the genetic associations of birthweight and childhood and adult body mass index (BMI) on the adult testosterone levels (bioavailable testosterone [BT], sex hormone-binding globulin [SHBG], and total testosterone [TT]) in women and men. Random-effect inverse-variance weighted (IVW) and 7 sensitivity analyses were performed. Data for weight traits were collected from large-scale genome-wide association studies (GWAS) ranging from 39 620 to 434 794 individuals. Summarized data for testosterone levels were obtained from a GWAS up to 230 454 individuals. Higher adult BMI are significantly associated with lower BT (β = -0.13; 95% CI, -0.16 to -0.09) and TT in men (β = -0.25; 95% CI, -0.30 to -0.20). On the contrary, higher adult BMI increased the levels of BT (β = 0.23; 95% CI, 0.23 to 0.20) and TT (β = 0.04; 95% CI, 0.01 to 0.07) in women. Similar genetic associations on testosterone levels with sexual differences were observed for childhood BMI. However, higher birthweight led to lower BT levels in adult men (β = -0.08; 95% CI, -0.12 to -0.03) and women (β = -0.07; 95% CI, -0.13 to -0.02). Our study supports that birthweight, childhood BMI, and adult BMI affect testosterone levels in men and women in adult life. The genetic associations of childhood BMI on testosterone levels are consistent with adult BMI, but not with birthweight.