Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis

Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone. Bi-directional Mendelian randomization (MR) analysis on prospe...

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Published in:PloS one Vol. 12; no. 4; p. e0176277
Main Authors: Eriksson, Joel, Haring, Robin, Grarup, Niels, Vandenput, Liesbeth, Wallaschofski, Henri, Lorentzen, Erik, Hansen, Torben, Mellström, Dan, Pedersen, Oluf, Nauck, Matthias, Lorentzon, Mattias, Nystrup Husemoen, Lise Lotte, Völzke, Henry, Karlsson, Magnus, Baumeister, Sebastian E., Linneberg, Allan, Ohlsson, Claes
Format: Journal Article
Language:English
Published: United States Public Library of Science 2017
Public Library of Science (PLoS)
Subjects:
Adolescent
Adult
Aged
Androgens
Biology and Life Sciences
Body mass
Body Mass Index
Body size
Body weight
Clinical Medicine
Consortia
elderly-men
fto gene
Genetic Predisposition to Disease
genome-wide association
hormone-binding globulin
Humans
hypogonadotropic hypogonadism
Klinisk medicin
Male
Medicine and Health Sciences
Men
Mendelian Randomization Analysis
Meta-analysis
metabolic syndrome
muscle strength
Obesity
Obesity - blood
Obesity - genetics
older men
Phenotype
Physical Sciences
Polymorphism, Single Nucleotide
Preventive medicine
Randomization
Research and Analysis Methods
risk-factors
Science & Technology - Other Topics
Ships
Single-nucleotide polymorphism
Smoking
Social Sciences
Studies
Testosterone
Testosterone - blood
Weight reduction
Young Adult
Denmark
Sweden
Germany
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone. Bi-directional Mendelian randomization (MR) analysis on prospective cohorts. Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden). 7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs. BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site. 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). 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.
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Competing Interests: The authors have declared that no competing interests exist.
Conceptualization: JE RH AL CO.Data curation: JE RH AL CO.Formal analysis: JE RH NG LV HW EL TH DM OP MN ML LLNH HV MK SEB AL CO.Funding acquisition: RH AL CO.Investigation: JE EL CO.Methodology: JE RH LV AL CO.Project administration: JE RH AL CO.Resources: JE RH LV AL CO.Software: JE EL.Supervision: JE RH AL CO.Validation: JE RH AL CO.Visualization: JE RH AL CO.Writing – original draft: JE RH LV AL CO.Writing – review & editing: JE RH NG LV HW EL TH DM OP MN ML LLNH HV MK SEB AL CO.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0176277