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Article: Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization investigation

TitleGenetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization investigation
Authors
KeywordsCausal inference
Disease aetiology
Genetic epidemiology
Mendelian randomization
Sex hormones
Testosterone
Issue Date2018
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/ijcard
Citation
International Journal of Cardiology, 2018, v. 267, p. 171-176 How to Cite?
AbstractBackground: Testosterone supplementation has been linked to increased cardiovascular disease risk in some observational studies. The causal role of testosterone can be investigated using a Mendelian randomization approach. Methods and results: We assessed genetic associations of variants in two gene regions (SHBG and JMJD1C) with several cardiovascular risk factors (lipids, adiponectin, blood pressure, anthropometric traits) plus male pattern baldness, including control outcomes and potential mediators. We assessed genetic associations with coronary artery disease (CAD) risk in the CARDIoGRAMplusC4D consortium (171,191 individuals including 60,801 cases), and associations with CAD and ischaemic stroke risk in the UK Biobank (367,643 individuals including 25,352 CAD cases and 3650 ischaemic stroke cases). Genetic predictors of increased serum testosterone were associated with lipids, blood pressure, and height. There was some evidence of an association with risk of CAD (SHBG gene region: odds ratio (OR) 0.95 per 1 unit increase in log-transformed testosterone [95% confidence interval: 0.81–1.12, p = 0.55]; JMJD1C gene region: OR 1.24 [1.01–1.51, p = 0.04]) and ischaemic stroke both overall (SHBG: OR 1.05 [0.64, 1.73, p = 0.83]; JMJD1C: OR 2.52 [1.33, 4.77, p = 0.005]) and in men. However, associations with some control outcomes were in the opposite direction to that expected. Conclusions: Sex hormone-related mechanisms appear to be relevant to cardiovascular risk factors and for stroke (particularly for men). However, the extent that these findings are specifically informative about endogenous testosterone or testosterone supplementation is unclear. These findings underline a fundamental limitation for the use of Mendelian randomization where biological knowledge about the function of genetic variants is uncertain.
Persistent Identifierhttp://hdl.handle.net/10722/261597
ISSN
2023 Impact Factor: 3.2
2023 SCImago Journal Rankings: 1.126
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSchooling, CM-
dc.contributor.authorLuo, S-
dc.contributor.authorAu Yeung, SLR-
dc.contributor.authorThompson, DJ-
dc.contributor.authorKarthikeyan, S-
dc.contributor.authorBolton, TR-
dc.contributor.authorMason, AM-
dc.contributor.authorIngelsson, E-
dc.contributor.authorBurgess, S-
dc.date.accessioned2018-09-28T04:44:25Z-
dc.date.available2018-09-28T04:44:25Z-
dc.date.issued2018-
dc.identifier.citationInternational Journal of Cardiology, 2018, v. 267, p. 171-176-
dc.identifier.issn0167-5273-
dc.identifier.urihttp://hdl.handle.net/10722/261597-
dc.description.abstractBackground: Testosterone supplementation has been linked to increased cardiovascular disease risk in some observational studies. The causal role of testosterone can be investigated using a Mendelian randomization approach. Methods and results: We assessed genetic associations of variants in two gene regions (SHBG and JMJD1C) with several cardiovascular risk factors (lipids, adiponectin, blood pressure, anthropometric traits) plus male pattern baldness, including control outcomes and potential mediators. We assessed genetic associations with coronary artery disease (CAD) risk in the CARDIoGRAMplusC4D consortium (171,191 individuals including 60,801 cases), and associations with CAD and ischaemic stroke risk in the UK Biobank (367,643 individuals including 25,352 CAD cases and 3650 ischaemic stroke cases). Genetic predictors of increased serum testosterone were associated with lipids, blood pressure, and height. There was some evidence of an association with risk of CAD (SHBG gene region: odds ratio (OR) 0.95 per 1 unit increase in log-transformed testosterone [95% confidence interval: 0.81–1.12, p = 0.55]; JMJD1C gene region: OR 1.24 [1.01–1.51, p = 0.04]) and ischaemic stroke both overall (SHBG: OR 1.05 [0.64, 1.73, p = 0.83]; JMJD1C: OR 2.52 [1.33, 4.77, p = 0.005]) and in men. However, associations with some control outcomes were in the opposite direction to that expected. Conclusions: Sex hormone-related mechanisms appear to be relevant to cardiovascular risk factors and for stroke (particularly for men). However, the extent that these findings are specifically informative about endogenous testosterone or testosterone supplementation is unclear. These findings underline a fundamental limitation for the use of Mendelian randomization where biological knowledge about the function of genetic variants is uncertain.-
dc.languageeng-
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/ijcard-
dc.relation.ispartofInternational Journal of Cardiology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCausal inference-
dc.subjectDisease aetiology-
dc.subjectGenetic epidemiology-
dc.subjectMendelian randomization-
dc.subjectSex hormones-
dc.subjectTestosterone-
dc.titleGenetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization investigation-
dc.typeArticle-
dc.identifier.emailSchooling, CM: cms1@hkucc.hku.hk-
dc.identifier.emailAu Yeung, SLR: ayslryan@hku.hk-
dc.identifier.authoritySchooling, CM=rp00504-
dc.identifier.authorityAu Yeung, SLR=rp02224-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ijcard.2018.05.051-
dc.identifier.pmid29804699-
dc.identifier.pmcidPMC6024225-
dc.identifier.scopuseid_2-s2.0-85047425868-
dc.identifier.hkuros291974-
dc.identifier.volume267-
dc.identifier.spage171-
dc.identifier.epage176-
dc.identifier.isiWOS:000436570700040-
dc.publisher.placeIreland-
dc.identifier.issnl0167-5273-

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