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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape.
Ried, Janina S; Jeff M, Janina; Chu, Audrey Y; Bragg-Gresham, Jennifer L; van Dongen, Jenny; Huffman, Jennifer E; Ahluwalia, Tarunveer S; Cadby, Gemma; Eklund, Niina; Eriksson, Joel; Esko, Tõnu; Feitosa, Mary F; Goel, Anuj; Gorski, Mathias; Hayward, Caroline; Heard-Costa, Nancy L; Jackson, Anne U; Jokinen, Eero; Kanoni, Stavroula; Kristiansson, Kati; Kutalik, Zoltán; Lahti, Jari; Luan, Jian'an; Mägi, Reedik; Mahajan, Anubha; Mangino, Massimo; Medina-Gomez, Carolina; Monda, Keri L; Nolte, Ilja M; Pérusse, Louis; Prokopenko, Inga; Qi, Lu; Rose, Lynda M; Salvi, Erika; Smith, Megan T; Snieder, Harold; Stancáková, Alena; Ju Sung, Yun; Tachmazidou, Ioanna; Teumer, Alexander; Thorleifsson, Gudmar; van der Harst, Pim; Walker, Ryan W; Wang, Sophie R; Wild, Sarah H; Willems, Sara M; Wong, Andrew; Zhang, Weihua; Albrecht, Eva; Couto Alves, Alexessander.
Affiliation
  • Ried JS; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Jeff M J; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • Chu AY; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
  • Bragg-Gresham JL; Kidney Epidemiology and Cost Center, Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • van Dongen J; Department of Biological Psychology, VU University, 1081BT Amsterdam, The Netherlands.
  • Huffman JE; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU Edinburgh, Scotland.
  • Ahluwalia TS; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, 2100 Copenhagen, Denmark.
  • Cadby G; Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark.
  • Eklund N; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé 34, DK-2820 Copenhagen, Denmark.
  • Eriksson J; Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia 6009, Australia.
  • Esko T; Department of Health, National Institute for Health and Welfare (THL), FI-00271 Helsinki, Finland.
  • Feitosa MF; Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
  • Goel A; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 2142, USA.
  • Gorski M; Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
  • Hayward C; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
  • Heard-Costa NL; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Jackson AU; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
  • Jokinen E; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
  • Kanoni S; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Kristiansson K; Department of Nephrology, University Hospital Regensburg, 93042 Regensburg, Germany.
  • Kutalik Z; Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, 93053 Regensburg, Germany.
  • Lahti J; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU Edinburgh, Scotland.
  • Luan J; National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA.
  • Mägi R; Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
  • Mahajan A; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Mangino M; Hospital for Children and Adolescents, University of Helsinki, FI-00290 Helsinki, Finland.
  • Medina-Gomez C; Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge CB10 1SA, UK.
  • Monda KL; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Nolte IM; Department of Health, National Institute for Health and Welfare (THL), FI-00271 Helsinki, Finland.
  • Pérusse L; Institute for Molecular Medicine Finland, University of Helsinki, FI-00290 Helsinki, Finland.
  • Prokopenko I; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
  • Qi L; Department of Medical Genetics, University of Lausanne, Lausanne, 1005, Switzerland.
  • Rose LM; Institute of Social and Preventive Medicine, University Hospital Lausanne (CHUV), 1010 Lausanne, Switzerland.
  • Salvi E; Folkhälsan Research Centre, FI-00290 Helsinki, Finland.
  • Smith MT; Institute of Behavioural Sciences, University of Helsinki, FI-00014 Helsinki, Finland.
  • Snieder H; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Stancáková A; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
  • Ju Sung Y; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Tachmazidou I; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Teumer A; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
  • Thorleifsson G; Department of Epidemiology, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands.
  • van der Harst P; Department of Internal Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands.
  • Walker RW; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Wang SR; The Center for Observational Research, Amgen Inc., Thousand Oaks, California 91320-1799, USA.
  • Wild SH; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
  • Willems SM; Department of Kinesiology, Laval University, Québec, Québec, Canada G1V 0A6.
  • Wong A; Institute of Nutrition and Functional Foods, Laval University, Québec, Québec, Canada G1V 0A6.
  • Zhang W; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Albrecht E; Department of Genomics of Common Disease, School of Public Health, Imperial College London, London W12 0NN, UK.
  • Couto Alves A; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Nat Commun ; 7: 13357, 2016 11 23.
Article in En | MEDLINE | ID: mdl-27876822
Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Anthropometry / Principal Component Analysis / Body Size / Models, Genetic Type of study: Prognostic_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2016 Document type: Article Affiliation country: Germany Country of publication: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Anthropometry / Principal Component Analysis / Body Size / Models, Genetic Type of study: Prognostic_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2016 Document type: Article Affiliation country: Germany Country of publication: United kingdom