TY - JOUR
T1 - Causal relationship between obesity and serum testosterone status in men
T2 - A bidirectional 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 - Husemoen, Lise Lotte Nystrup
AU - Völzke, Henry
AU - Karlsson, Magnus
AU - Baumeister, Sebastian E.
AU - Linneberg, Allan
AU - Ohlsson, Claes
PY - 2017/4/1
Y1 - 2017/4/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85018325539&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0176277
DO - 10.1371/journal.pone.0176277
M3 - Article
C2 - 28448539
AN - SCOPUS:85018325539
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0176277
ER -