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

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  • Joel Eriksson
  • Robin Haring
  • Niels Grarup
  • Liesbeth Vandenput
  • Henri Wallaschofski
  • Erik Lorentzen
  • Torben Hansen
  • Dan Mellström
  • Oluf Pedersen
  • Matthias Nauck
  • Mattias Lorentzon
  • Lise Lotte Nystrup Husemoen
  • Henry Völzke
  • Magnus Karlsson
  • Sebastian E Baumeister
  • Allan Linneberg
  • Claes Ohlsson
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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.

Original languageEnglish
JournalP L o S One
Issue number4
Pages (from-to)e0176277
Publication statusPublished - 2017

    Research areas

  • Adolescent, Adult, Aged, Body Mass Index, Genetic Predisposition to Disease, Humans, Male, Mendelian Randomization Analysis, Obesity, Phenotype, Polymorphism, Single Nucleotide, Testosterone, Young Adult, Journal Article

ID: 51732204