The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Thomas W Winkler; Anne E Justice; Mariaelisa Graff; Llilda Barata; Mary F Feitosa; Su Chu; Jacek Czajkowski; Tõnu Esko; Tove Fall; Tuomas O Kilpeläinen; Yingchang Lu; Reedik Mägi; Evelin Mihailov; Tune H Pers; Sina Rüeger; Alexander Teumer; Georg B Ehret; Teresa Ferreira; Nancy L Heard-Costa; Juha Karjalainen; Vasiliki Lagou; Anubha Mahajan; Michael D Neinast; Inga Prokopenko; Jeannette Simino; Tanya M Teslovich; Rick Jansen; Harm-Jan Westra; Charles C White; Devin Absher; Tarunveer S Ahluwalia; Shafqat Ahmad; Eva Albrecht; Alexessander Couto Alves; Jennifer L Bragg-Gresham; Anton J M de Craen; Joshua C Bis; Amélie Bonnefond; Gabrielle Boucher; Gemma Cadby; Yu-Ching Cheng; Charleston W K Chiang; Graciela Delgado; Ayse Demirkan; Nicole Dueker; Niina Eklund; Gudny Eiriksdottir; Joel Eriksson; Bjarke Feenstra; Krista Fischer; Francesca Frau; Tessel E Galesloot; Frank Geller; Anuj Goel; Mathias Gorski; Tanja B Grammer; Stefan Gustafsson; Saskia Haitjema; Jouke-Jan Hottenga; Jennifer E Huffman; Anne U Jackson; Kevin B Jacobs; Åsa Johansson; Marika Kaakinen; Marcus E Kleber; Jari Lahti; Irene Mateo Leach; Benjamin Lehne; Youfang Liu; Ken Sin Lo; Mattias Lorentzon; Jian'an Luan; Pamela A F Madden; Massimo Mangino; Barbara McKnight; Carolina Medina-Gomez; Keri L Monda; May E Montasser; Gabriele Müller; Martina Müller-Nurasyid; Ilja M Nolte; Kalliope Panoutsopoulou; Laura Pascoe; Lavinia Paternoster; Nigel W Rayner; Frida Renström; Federica Rizzi; Lynda M Rose; Kathy A Ryan; Perttu Salo; Serena Sanna; Hubert Scharnagl; Jianxin Shi; Albert Vernon Smith; Lorraine Southam; Alena Stančáková; Valgerdur Steinthorsdottir; Rona J Strawbridge; Yun Ju Sung; Ioanna Tachmazidou; DIAGRAM Consortium

doi:10.1371/journal.pgen.1005378

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The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

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The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, …

PLoS genetics, Vol.11(10), pp.e1005378-42

01/10/2015

DOI: https://doi.org/10.1371/journal.pgen.1005378

PMID: 26426971

Abstract

Adult

Age Factors

Aged

Body Mass Index

Body Size - genetics

Chromosome Mapping

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Male

Middle Aged

Polymorphism, Single Nucleotide

Sex Characteristics

Waist-Hip Ratio

White People

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.

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Title: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study
Creators: Thomas W Winkler - University of Regensburg
Anne E Justice - University of North Carolina at Chapel Hill
Mariaelisa Graff - University of North Carolina at Chapel Hill
Llilda Barata - Washington University in St. Louis
Mary F Feitosa - Washington University in St. Louis
Su Chu - Michigan United
Jacek Czajkowski - Washington University in St. Louis
Tõnu Esko - Broad Institute
Tove Fall - Science for Life Laboratory
Tuomas O Kilpeläinen - University of Copenhagen
Yingchang Lu - Icahn School of Medicine at Mount Sinai
Reedik Mägi - Centre for Human Genetics
Evelin Mihailov - Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia
Tune H Pers - Boston Children's Hospital
Sina Rüeger - Institute of Social and Preventive Medicine
Alexander Teumer - Universitätsmedizin Greifswald
Georg B Ehret - Johns Hopkins Medicine
Teresa Ferreira - University of Oxford
Nancy L Heard-Costa
Juha Karjalainen - University Medical Center Groningen
Vasiliki Lagou - Oxford Centre for Diabetes, Endocrinology and Metabolism
Anubha Mahajan - University of Oxford
Michael D Neinast - The University of Texas Southwestern Medical Center
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Jeannette Simino - Washington University in St. Louis
Tanya M Teslovich - University of Michigan–Ann Arbor
Rick Jansen - EMGO Institute for Health and Care Research
Harm-Jan Westra - Brigham and Women's Hospital
Charles C White - Boston University
Devin Absher - HudsonAlpha Institute for Biotechnology
Tarunveer S Ahluwalia - University of Copenhagen
Shafqat Ahmad - Skåne University Hospital
Eva Albrecht - Helmholtz Zentrum München
Alexessander Couto Alves - Imperial College London
Jennifer L Bragg-Gresham - University of Michigan–Ann Arbor
Anton J M de Craen - Leiden University Medical Center
Joshua C Bis - University of Washington
Amélie Bonnefond - European Genomic Institute for Diabetes
Gabrielle Boucher - Montreal Heart Institute
Gemma Cadby - University of Western Australia
Yu-Ching Cheng
Charleston W K Chiang - University of California, Los Angeles
Graciela Delgado - Heidelberg University
Ayse Demirkan - Erasmus MC
Nicole Dueker - University of Mary
Niina Eklund - University of Helsinki
Gudny Eiriksdottir - Icelandic Heart Association
Joel Eriksson - University of Gothenburg
Bjarke Feenstra - Statens Serum Institut
Krista Fischer - Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia
Francesca Frau - University of Milan
Tessel E Galesloot - Radboud University Nijmegen
Frank Geller - Statens Serum Institut
Anuj Goel - University of Oxford
Mathias Gorski - University Hospital Regensburg
Tanja B Grammer - Heidelberg University
Stefan Gustafsson - Uppsala University
Saskia Haitjema - Utrecht University
Jouke-Jan Hottenga - University of Amsterdam
Jennifer E Huffman - University of Edinburgh
Anne U Jackson - University of Michigan–Ann Arbor
Kevin B Jacobs - Science Applications International Corporation
Åsa Johansson - Uppsala University
Marika Kaakinen - Imperial College London
Marcus E Kleber - University Hospital Heidelberg
Jari Lahti - University of Helsinki
Irene Mateo Leach - University Medical Center Groningen
Benjamin Lehne - Imperial College London
Youfang Liu - University of North Carolina at Chapel Hill
Ken Sin Lo - Montreal Heart Institute
Mattias Lorentzon - University of Gothenburg
Jian'an Luan - University of Cambridge
Pamela A F Madden - Washington University in St. Louis
Massimo Mangino - King's College London
Barbara McKnight - University of Washington
Carolina Medina-Gomez - Erasmus MC
Keri L Monda - University of North Carolina at Chapel Hill
May E Montasser - University of Maryland, Baltimore
Gabriele Müller - University Hospital Carl Gustav Carus
Martina Müller-Nurasyid
Ilja M Nolte - University Medical Center Groningen
Kalliope Panoutsopoulou - Wellcome Sanger Institute
Laura Pascoe - Newcastle University
Lavinia Paternoster - University of Bristol
Nigel W Rayner - Oxford Centre for Diabetes, Endocrinology and Metabolism
Frida Renström - Skåne University Hospital
Federica Rizzi - Fondazione Filarete
Lynda M Rose - Brigham and Women's Hospital
Kathy A Ryan - Genomic
Perttu Salo - Finnish Institute for Health and Welfare
Serena Sanna - Institute of Genetic and Biomedical Research
Hubert Scharnagl - Medical University of Graz
Jianxin Shi - National Cancer Institute
Albert Vernon Smith - Icelandic Heart Association
Lorraine Southam - University of Oxford
Alena Stančáková - Kuopio University Hospital
Valgerdur Steinthorsdottir - deCODE Genetics
Rona J Strawbridge - Karolinska Institutet
Yun Ju Sung - Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America
Ioanna Tachmazidou - Wellcome Sanger Institute
DIAGRAM Consortium
Publication Details: PLoS genetics, Vol.11(10), pp.e1005378-42
Publication Date: 01/10/2015
Grant note: R01 HL045670 / NHLBI NIH HHS R01 DK062370 / NIDDK NIH HHS U01 DK062418 / NIDDK NIH HHS R01 DA012854 / NIDA NIH HHS U01 HL105198 / NHLBI NIH HHS R01 NS045012 / NINDS NIH HHS R01 DK072193 / NIDDK NIH HHS R01 DK091718 / NIDDK NIH HHS U01 HG004402 / NHGRI NIH HHS R01 AA013321 / NIAAA NIH HHS
Identifiers: 99928683102346; WOS:000364401600002
Academic Unit: School of Biosciences; Institute for Sustainability; Surrey Institute for People-Centred AI
Language: English
Resource Type: Journal article

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

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