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Record W2147774366 · doi:10.1371/journal.pgen.1003500

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

2013· article· en· W2147774366 on OpenAlexaff
Joshua C. Randall, Thomas W. Winkler, Zoltán Kutalik, Sonja I. Berndt, Anne Jackson, Keri L. Monda, Tuomas O. Kilpeläinen, Tõnu Esko, Reedik Mägi, Shengxu Li, Tsegaselassie Workalemahu, Mary F. Feitosa, Damien C. Croteau‐Chonka, Felix R. Day, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Adam E. Locke, Iain Mathieson, André Scherag, Sailaja Vedantam, Andrew R. Wood, Liming Liang, Valgerður Steinthórsdóttir, Guðmar Þorleifsson, Emmanouil T. Dermitzakis, Antigone S. Dimas, Fredrik Karpe, Josine L. Min, Deborah J. Clegg, Thomas N. Person, Jon P. Krohn, Sabrina Bauer, Christa Buechler, Kristina Eisinger, Amélie Bonnefond, Philippe Froguel, Jouke‐Jan Hottenga, Inga Prokopenko, Lindsay L. Waite, Tamara B. Harris, Albert V. Smith, Alan R. Shuldiner, Wendy L. McArdle, Mark J. Caulfield, Patricia B. Munroe, Henrik Grönberg, Yii-Der Ida Chen, Li Guo, J. Beckmann, Toby Johnson, Unnur Þorsteinsdóttir, Maris Teder‐Laving, Kay‐Tee Khaw, Nicholas J. Wareham, Wei Zhao, Najaf Amin, Ben A. Oostra, Aldi T. Kraja, Michael A. Province, L. Adrienne Cupples, Nancy L. Heard‐Costa, Jaakko Kaprio, Samuli Ripatti, Ida Surakka, Francis S. Collins, Jouko Saramies, Jaakko Tuomilehto, Antti Jula, Veikko Salomaa, Jeanette Erdmann, Christian Hengstenberg, Christina Loley, Heribert Schunkert, Claudia Lamina, H.-Erich Wichmann, Eva Albrecht, Christian Gieger, Andrew A. Hicks, Åsa Johansson, Peter P. Pramstaller, Sekar Kathiresan, Elizabeth K. Speliotes, Brenda W.J.H. Penninx, Anna-Liisa Hartikainen, Marjo‐Riitta Järvelin, Ulf Gyllensten, Dorret I. Boomsma, Harry Campbell, James F. Wilson, Stephen J. Chanock, Martin Farrall, Anuj Goel, Carolina Medina‐Gómez, Fernando Rivadeneira, Karol Estrada, André G. Uitterlinden, Albert Hofman, M. Carola Zillikens, Martin den Heijer, Lambertus A. Kiemeney, Andrea Maschio, Per Hall, Jonathan P. Tyrer, Alexander Teumer, Henry Völzke, Péter Kovács, Anke Tönjes, Massimo Mangino, Tim D. Spector, Caroline Hayward, Igor Rudan, Alistair S. Hall, Nilesh J. Samani, Antony Attwood, Jennifer G. Sambrook, Joseph Hung, Lyle J. Palmer, Marja‐Liisa Lokki, Juha Sinisalo, Gabrielle Boucher, Heikki V. Huikuri, Mattias Lorentzon, Claes Ohlsson, Niina Eklund, Johan G. Eriksson, Cristina Barlassina, Carlo Rivolta, Ilja M. Nolte, Harold Snieder, Melanie M. van der Klauw, Jana V. van Vliet‐Ostaptchouk, Pablo V. Gejman, Jianxin Shi, Kevin B. Jacobs, Stephan J. L. Bakker, Irene Mateo Leach, Gerjan Navis, Pim van der Harst, Nicholas G. Martin, Sarah E. Medland, Grant W. Montgomery, Jian Yang, Daniel I. Chasman, Paul M. Ridker, Lynda M. Rose, Terho Lehtimäki, Olli T. Raitakari, Devin Absher, Carlos Iribarren, Hanneke Basart, Kees Hovingh, Elina Hyppönen, Chris Power, Denise Anderson, John Beilby, Jennie Hui, Jennifer Jolley, Hendrik B. Sager, Stefan R. Bornstein, Peter Schwarz, Kati Kristiansson, Markus Perola, Jaana Lindström, Amy J. Swift, Matti Uusitupa, Mustafa Atalay, Timo A. Lakka, Rainer Rauramaa, Jennifer L. Bolton, Gerry Fowkes, Ross M. Fraser, Jackie F. Price, Krista Fischer, Kaarel KrjutÅ¡kov, Andres Metspalu, Evelin Mihailov, Claudia Langenberg, Jian’an Luan, Ken K. Ong, Peter S. Chines, Sirkka Keinänen‐Kiukaanniemi, Timo Saaristo, Sarah Edkins, Paul W. Franks, Göran Hallmans, Dmitry Shungin, Andrew David Morris, Raimund Erbel, Susanne Moebus, Markus M. Nöthen, Sonali Pechlivanis, Kristian Hveem, Narisu Narisu, Anders Hamsten, Steve E. Humphries, Rona J. Strawbridge, Elena Tremoli, Harald Grallert, Barbara Thorand, Thomas Illig, Wolfgang Köenig, Martina Müller‐Nurasyid, Annette Peters, Bernhard O. Boehm, Marcus E. Kleber, Winfried März, Bernhard R. Winkelmann, Johanna Kuusisto, Markku Laakso, Dominique Arveiler, Giancarlo Cesana, Kari Kuulasmaa, Jarmo Virtamo, J. W. G. Yarnell, Diana Kuh, Andrew Wong, Lars Lind, Ulf dé Fairé, Bruna Gigante, Patrik K. E. Magnusson, Nancy L. Pedersen, George Dedoussis, Maria Dimitriou, Genovefa Kolovou, Stavroula Kanoni, Kathleen Stirrups, Lori L. Bonnycastle, Inger Njølstad, Tom Wilsgaard, Andrea Ganna, Emil Rehnberg, Aroon D. Hingorani, Mika Kivimäki, Meena Kumari, Themistocles L. Assimes, Inês Barroso, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Caroline S. Fox, Timothy M. Frayling, Talin Haritunians, David J. Hunter, Erik Ingelsson, Robert C. Kaplan, Karen L. Mohlke, Jeffrey R. O’Connell, David Schlessinger, David P. Strachan, Kāri Stefánsson, Cornelia M. van Duijn, Gonçalo R. Abecasis, Mark I. McCarthy, Joel N. Hirschhorn, Lu Qi, Ruth J. F. Loos, Cecilia M. Lindgren, Kari E. North, Iris M. Heid

Bibliographic record

VenuePLoS Genetics · 2013
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMontreal Heart InstituteLunenfeld-Tanenbaum Research InstituteOntario Institute for Cancer Research
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Research ResourcesBritish Heart FoundationU.S. National Library of MedicineNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute on Drug AbuseNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute for Health and Care ResearchNational Institute on AgingAgency for Healthcare Research and QualityEconomic and Social Research CouncilNational Center for Advancing Translational SciencesMedical Research CouncilWellcome TrustCancer Research UKNovo Nordisk FondenNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Institute of General Medical SciencesNational Human Genome Research InstituteNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Cancer InstituteNational Institute on Alcohol Abuse and Alcoholism
KeywordsBiologySexual dimorphismGenome-wide association studyAnthropometryWaistGeneticsCircumferenceSingle-nucleotide polymorphismWaist–hip ratioLocus (genetics)Genetic associationBody mass indexZoologyInternal medicineGenotypeMedicineGeneEndocrinology

Abstract

fetched live from OpenAlex

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.058
GPT teacher head0.307
Teacher spread0.249 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations459
Published2013
Admission routes1
Has abstractyes

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