TY - JOUR

T1 - Causal relationship between obesity and serum testosterone status in men

T2 - A bi-directional mendelian randomization analysis

AU - Eriksson, Joel

AU - Haring, Robin

AU - Grarup, Niels

AU - Vandenput, Liesbeth

AU - Wallaschofski, Henri

AU - Lorentzen, Erik

AU - Hansen, Torben

AU - Mellström, Dan

AU - Pedersen, Oluf

AU - Nauck, Matthias

AU - Lorentzon, Mattias

AU - Nystrup Husemoen, Lise Lotte

AU - Völzke, Henry

AU - Karlsson, Magnus

AU - Baumeister, Sebastian E

AU - Linneberg, Allan

AU - Ohlsson, Claes

PY - 2017

Y1 - 2017

N2 - CONTEXT: Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.OBJECTIVES: Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone.DESIGN: Bi-directional Mendelian randomization (MR) analysis on prospective cohorts.SETTING: Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden).PARTICIPANTS: 7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs.MAIN OUTCOME MEASURES: BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site.RESULTS: 1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum testosterone. No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349).CONCLUSIONS: Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men.

AB - CONTEXT: Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.OBJECTIVES: Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone.DESIGN: Bi-directional Mendelian randomization (MR) analysis on prospective cohorts.SETTING: Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden).PARTICIPANTS: 7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs.MAIN OUTCOME MEASURES: BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site.RESULTS: 1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum testosterone. No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349).CONCLUSIONS: Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men.

KW - Adolescent

KW - Adult

KW - Aged

KW - Body Mass Index

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Mendelian Randomization Analysis

KW - Obesity

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Testosterone

KW - Young Adult

KW - Journal Article

U2 - 10.1371/journal.pone.0176277

DO - 10.1371/journal.pone.0176277

M3 - Journal article

C2 - 28448539

VL - 12

SP - e0176277

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 4

ER -