Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Eriksson J

PROVIDER: S-EPMC5407807 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

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

Eriksson Joel J Haring Robin R Grarup Niels N Vandenput Liesbeth L Wallaschofski Henri H Lorentzen Erik E Hansen Torben T Mellström Dan D Pedersen Oluf O Nauck Matthias M Lorentzon Mattias M Nystrup Husemoen Lise Lotte LL Völzke Henry H Karlsson Magnus M Baumeister Sebastian E SE Linneberg Allan A Ohlsson Claes C

PloS one 20170427 4

<h4>Context</h4>Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.<h4>Objectives</h4>Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone.<h4>Design</h4>Bi-directional Mendelian randomization (MR) analysis on prospective cohorts.<h4>Setting</h4>Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden).<h4>Participants</h4>7446 ...[more]

PMID: 28448539

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Project description:BackgroundObesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.Methods and findingsWe used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n?=?123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p?=?6.52×10?²?). The BMI allele score was associated both with BMI (p?=?6.30×10??²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p?=?0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p?8.07×10??? for both scores) but not with BMI (synthesis score, p?=?0.88; metabolism score, p?=?0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p?=?0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p?0.57 for both vitamin D scores).ConclusionsOn the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Project description:BackgroundPrevious studies have shown that osteoarthritis (OA) and sarcopenia (SP) are closely related to each other, but the causal relationships between them have not been established. The aim of this study was to investigate the causal associations between OA and SP via a bi-directional Mendelian randomization (MR) approach.MethodsA bi-directional two-sample MR was adopted to research the causal relationship between SP and OA. The instrumental variables for SP and four types of OA: KOA, HOA, total knee replacement (TKR) and total hip replacement (THR) were derived from published large genome-wide association studies (GWAS). The inverse variance weighted (IVW), MR-Egger and weighted median estimator (WME) methods were used to estimate bi-directional causal effects.ResultsLow grip strength (GS) did not have a causal effect on four types of OA (KOA: OR = 1.205, 95% CI 0.837-1.734, p = 0.316; HOA: OR = 1.090, 95% CI 0.924-1.609, p = 0.307; TKR: OR = 1.190, 95% CI 1.084-1.307, p = 0.058; THR: OR = 1.035, 95% CI 0.792-1.353, p = 0.798), while appendicular lean mass (ALM) had a causal effect on four types of OA (KOA: OR = 1.104, 95% CI 1.041-1.171, p = 0.001; HOA: OR = 1.151, 95% CI 1.071-1.237, p < 0.001; TKR: OR = 1.114, 95% CI 1.007-1.232, p < 0.001; THR: OR = 1.203, 95% CI 1.099-1.316, p < 0.001). In the reverse direction, KOA or HOA did not have a significant causal effect on both GS and ALM (KOA-GS: OR = 1.077, 95% CI 0.886-1.309, p = 0.458; KOA-ALM: Beta = 0.004, p = 0.892; HOA-GS: OR = 1.038, 95% CI 0.981-1.099, p = 0.209; HOA-ALM: Beta = - 0.017, p = 0.196; TKR-GS: OR = 0.999, 95% CI 0.739-1.351, p = 0.997; TKR-ALM: Beta = 0.018, p = 0.501; THR-GS: OR = 1.037, 95% CI 0.978-1.101, p = 0.222; THR-ALM: Beta = - 0.023, p = 0.081).ConclusionsThe present study suggests that SP may have a causal effect on OA through changes in muscle composition rather than muscle strength, while little evidence was provided for the causal effect of OA on SP.

Dataset Information

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

Context

Objectives

Design

Setting

Participants

Main outcome measures

Results

Conclusions

Publications

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

Similar Datasets

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