The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study

2.50
Hdl Handle:
http://hdl.handle.net/11287/618136
Title:
The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study
Authors:
Winkler, T. [et al]; Hattersley, Andrew T.
Abstract:
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
Citation:
The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study. 2015. PLos Genetics 11(10):e1005378
Publisher:
PLoS
Journal:
PLoS Genetics
Issue Date:
1-Oct-2015
URI:
http://hdl.handle.net/11287/618136
DOI:
10.1371/journal.pgen.1005378
PubMed ID:
26426971
PubMed Central ID:
PMC4591371
Additional Links:
http://dx.plos.org/10.1371/journal.pgen.1005378
Note:
This article is freely available via the publisher's website, click on the 'Additional Link' above to access the full text.
Type:
Journal Article; Meta-Analysis
Language:
en
Appears in Collections:
2015 RD&E publications; Diabetes/Endocrine Services

Full metadata record

DC FieldValue Language
dc.contributor.authorWinkler, T. [et al]en
dc.contributor.authorHattersley, Andrew T.en
dc.date.accessioned2016-08-09T14:43:32Z-
dc.date.available2016-08-09T14:43:32Z-
dc.date.issued2015-10-01-
dc.identifier.citationThe influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study. 2015. PLos Genetics 11(10):e1005378en
dc.identifier.pmid26426971-
dc.identifier.doi10.1371/journal.pgen.1005378-
dc.identifier.urihttp://hdl.handle.net/11287/618136-
dc.description.abstractGenome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.en
dc.language.isoenen
dc.publisherPLoSen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pgen.1005378en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleThe influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction studyen
dc.typeJournal Articleen
dc.typeMeta-Analysisen
dc.identifier.journalPLoS Geneticsen
dc.identifier.pmcidPMC4591371-
dc.description.noteThis article is freely available via the publisher's website, click on the 'Additional Link' above to access the full text.en
dc.type.versionPublisheden

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