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
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Abstract	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.
AbstractList	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 = 2.810−3). 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. 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 = 2.810-3). 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. 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 = 2.810−3). 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. 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 = 2.810-3). 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. Context 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 = 2.810(-3)). For a body weight reduction altering the BMI from 30 to 25 kg/m(2), 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. Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.CONTEXTObesity 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.OBJECTIVESExamine the direction and causality of the relationship between body mass index (BMI) and serum testosterone.Bi-directional Mendelian randomization (MR) analysis on prospective cohorts.DESIGNBi-directional Mendelian randomization (MR) analysis on prospective cohorts.Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden).SETTINGFive 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.PARTICIPANTS7446 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.MAIN OUTCOME MEASURESBMI 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 = 2.810-3). 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).RESULTS1 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.CONCLUSIONSOur 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.
Author	Grarup, Niels Völzke, Henry Lorentzon, Mattias Karlsson, Magnus Haring, Robin Lorentzen, Erik Pedersen, Oluf Linneberg, Allan Hansen, Torben Eriksson, Joel Vandenput, Liesbeth Ohlsson, Claes Nystrup Husemoen, Lise Lotte Nauck, Matthias Wallaschofski, Henri Mellström, Dan Baumeister, Sebastian E.
AuthorAffiliation	1 Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 8 University Medicine Greifswald, Institute for Community Medicine, Greifswald, Germany 3 School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia 6 Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden 2 University Medicine Greifswald, Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany Shanghai Diabetes Institute, CHINA 10 Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany 9 Clinical and Molecular Osteoporosis Research Unit, Department of Orthopaedics and Clinical Sciences, Lund University, Skåne University Hospital (SUS), Malmö, Sweden 4 The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copen
AuthorAffiliation_xml	– name: 8 University Medicine Greifswald, Institute for Community Medicine, Greifswald, Germany – name: 5 Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden – name: 3 School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia – name: 12 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – name: 2 University Medicine Greifswald, Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany – name: 4 The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – name: Shanghai Diabetes Institute, CHINA – name: 10 Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany – name: 1 Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden – name: 6 Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden – name: 7 Research Centre for Prevention and Health, the Capital Region, Copenhagen, Denmark – name: 9 Clinical and Molecular Osteoporosis Research Unit, Department of Orthopaedics and Clinical Sciences, Lund University, Skåne University Hospital (SUS), Malmö, Sweden – name: 11 Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark
Author_xml	– sequence: 1 givenname: Joel surname: Eriksson fullname: Eriksson, Joel – sequence: 2 givenname: Robin surname: Haring fullname: Haring, Robin – sequence: 3 givenname: Niels surname: Grarup fullname: Grarup, Niels – sequence: 4 givenname: Liesbeth surname: Vandenput fullname: Vandenput, Liesbeth – sequence: 5 givenname: Henri surname: Wallaschofski fullname: Wallaschofski, Henri – sequence: 6 givenname: Erik surname: Lorentzen fullname: Lorentzen, Erik – sequence: 7 givenname: Torben surname: Hansen fullname: Hansen, Torben – sequence: 8 givenname: Dan surname: Mellström fullname: Mellström, Dan – sequence: 9 givenname: Oluf surname: Pedersen fullname: Pedersen, Oluf – sequence: 10 givenname: Matthias surname: Nauck fullname: Nauck, Matthias – sequence: 11 givenname: Mattias surname: Lorentzon fullname: Lorentzon, Mattias – sequence: 12 givenname: Lise Lotte surname: Nystrup Husemoen fullname: Nystrup Husemoen, Lise Lotte – sequence: 13 givenname: Henry surname: Völzke fullname: Völzke, Henry – sequence: 14 givenname: Magnus surname: Karlsson fullname: Karlsson, Magnus – sequence: 15 givenname: Sebastian E. surname: Baumeister fullname: Baumeister, Sebastian E. – sequence: 16 givenname: Allan surname: Linneberg fullname: Linneberg, Allan – sequence: 17 givenname: Claes surname: Ohlsson fullname: Ohlsson, Claes
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Copyright	2017 Eriksson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2017 Eriksson et al 2017 Eriksson et al
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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.
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Snippet	Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Examine the direction and... Context Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Objectives Examine the... Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.CONTEXTObesity in men is... Context Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Examine the direction... Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.Examine the direction and... Context Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Objectives Examine the...
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SubjectTerms	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
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Title	Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis
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Volume	12
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