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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Anne E. Justice, Thomas W. Winkler, Mary F. Feitosa, Misa Graff, Virginia Fisher, Kristin Young, Llilda Barata, Xuan Deng, Jacek Czajkowski, David Hadley, Julius S. Ngwa, Tarunveer S. Ahluwalia, Audrey Y. Chu, Nancy L. Heard‐Costa, Elise Lim, Jeremiah Perez, John D. Eicher, Zoltán Kutalik, Luting Xue, Anubha Mahajan, Frida Renström, Joseph Wu, Qibin Qi, Shafqat Ahmad, Tamuno Alfred, Najaf Amin, Lawrence F. Bielak, Amélie Bonnefond, Jennifer Bragg, Gemma Cadby, Martina Chittani, Scott Coggeshall, Tanguy Corre, Neşe Direk, Joel Eriksson, Krista Fischer, Mathias Gorski, Marie Neergaard Harder, Momoko Horikoshi, Tao Huang, Jennifer E. Huffman, Anne Jackson, Johanne Marie Justesen, Stavroula Kanoni, Leena Kinnunen, Marcus E. Kleber, Pirjo Komulainen, Meena Kumari, Unhee Lim, Jian’an Luan, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Martina Müller‐Nurasyid, Pau Navarro, Louis Përusse, Natalia Pervjakova, Cinzia Sarti, Albert V. Smith, Jennifer A. Smith, Alena Stančáková, Rona J. Strawbridge, Heather M. Stringham, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W. van der Laan, Peter J. van der Most, Jana V. van Vliet‐Ostaptchouk, Sailaja Vedantam, Niek Verweij, Jacqueline M. Vink, Véronique Vitart, Ying Wu, Loïc Yengo, Weihua Zhang, Jing Hua Zhao, Martina E. Zimmermann, Niha Zubair, Gonçalo R. Abecasis, Linda S. Adair, Saima Afaq, Uzma Afzal, Traci M. Bartz, John Beilby, Richard N. Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Eric Boerwinkle, Lori L. Bonnycastle, Erwin Böttinger, Daniele Braga, Brendan M. Buckley, Steven Buyske, Harry Campbell, John C. Chambers, Francis S. Collins, Joanne E. Curran, Gert J. de Borst, George Dedoussis, Graciela E. Delgado, Hester M. den Ruijter, Guðný Eiríksdóttir, Anna L. Eriksson, Tõnu Esko, Jessica D. Faul, Ian Ford, Terrence Forrester, Karl Gertow, Bruna Gigante, Nicola Glorioso, Jian Gong, Harald Grallert, Tanja B. Grammer, Niels Grarup, Saskia Haitjema, Göran Hallmans, Anders Hamsten, Torben Hansen, Tamara B. Harris, Catharina A. Hartman, Maija Hassinen, Nicholas D. Hastie, Andrew C. Heath, Dena Hernandez, Lucia A. Hindorff, Lynne J. Hocking, Mette Hollensted, Oddgeir L. Holmen, Georg Homuth, Jouke‐Jan Hottenga, Jie Huang, Joseph Hung, Nina Hutri‐Kähönen, Erik Ingelsson, Anthony James, John‐Olov Jansson, Min A. Jhun, Marit E. Jørgensen, Markus Juonala, Mika Kähönen, Magnus Karlsson, Heikki A. Koistinen, Ivana Kolčić, Genovefa Kolovou, Charles Kooperberg, Bernhard K. Krämer, Johanna Kuusisto, Kirsti Kvaløy, Timo A. Lakka, Claudia Langenberg, Lenore J. Launer, Karin Leander, Sang Lee, Lars Lind, Cecilia M. Lindgren, Allan Linneberg, Stéphane Lobbens, Marie Loh, Mattias Lorentzon, Robert Luben, Gitta H. Lubke, Anja Ludolph-Donislawski, Sara Lupoli, Reija Männikkö, Pedro Marques‐Vidal, Nicholas G. Martin, Colin A. McKenzie, Barbara McKnight, Dan Mellström, Cristina Menni, Grant W. Montgomery, A W Musk, Narisu Narisu, Matthias Nauck, Ilja M. Nolte, Albertine J. Oldehinkel, Matthias Olden, Ken K. Ong, Sandosh Padmanabhan, Patricia A. Peyser, Charlotta Pisinger, David J. Porteous, Olli T. Raitakari, Tuomo Rankinen, D. C. Rao, Laura J. Rasmussen‐Torvik, Rajesh Rawal, Treva Rice, Paul M. Ridker, Lynda M. Rose, Stephanie A. Bien, Igor Rudan, Serena Sanna, Mark A. Sarzynski, Naveed Sattar, Kai Savonen, David Schlessinger, Salome Scholtens, Claudia Schurmann, Robert A. Scott, Bengt Sennblad, Marten A. Siemelink, Günther Silbernagel, P. Eline Slagboom, Harold Snieder, Jan A. Staessen, David J. Stott, Morris A. Swertz, Amy J. Swift, Kent D. Taylor, Bamidele O. Tayo, Barbara Thorand, Dorothée Thuillier, Jaakko Tuomilehto, André G. Uitterlinden, Liesbeth Vandenput, Henry Völzke, Judith M. Vonk, Gérard Waeber, Mélanie Waldenberger, Sarah H. Wild, Gonneke Willemsen, Andrew Wong, Alan F. Wright, Wei Zhao, M. Carola Zillikens, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Carsten A. Böger, Dorret I. Boomsma, Claude Bouchard, Marcel Bruinenberg, Daniel I. Chasman, Peter S. Chines, Francesco Cucca, Daniele Cusi, Ulf dé Fairé, Luigi Ferrucci, Paul W. Franks, Philippe Froguel, Penny Gordon‐Larsen, Vilmundur Guðnason, Christopher A. Haiman, Caroline Hayward, Kristian Hveem, Andrew D. Johnson, J. Wouter Jukema, Mika Kivimäki, Jaspal S. Kooner, Diana Kuh, Markku Laakso, Terho Lehtimäki, Loı̈c Le Marchand, Winfried März, Mark I. McCarthy, Andres Metspalu, Andrew P. Morris, Claes Ohlsson, Lyle J. Palmer, Gerard Pasterkamp, Oluf Pedersen, Annette Peters, Ulrike Peters, Ozren Polašek, Bruce M. Psaty, Lu Qi, Rainer Rauramaa, Blair H. Smith, Konstantin Strauch, Henning Tiemeier, Elena Tremoli, Pim van der Harst, Henrik Vestergaard, Péter Vollenweider, Nicholas J. Wareham, David R. Weir, John B. Whitfield, James F. Wilson, Jessica Tyrrell, Timothy M. Frayling, Inês Barroso, Michael Boehnke, Panos Deloukas, Caroline S. Fox, Joel N. Hirschhorn, David J. Hunter, Tim D. Spector, David P. Strachan, Cornelia M. van Duijn, Iris M. Heid, Karen L. Mohlke, Jonathan Marchini, Tuomas O. Kilpeläinen, Ingrid B. Borecki, Kari E. North, L. Adrienne Cupples
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.
Bibliographic record
VenueTampere University Institutional Repository (Tampere University) · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicNutrition, Genetics, and Disease
Canadian institutionsnot available
FundersFP7 Ideas: European Research CouncilNational Institutes of HealthHjartaverndMedical Research CouncilTartu ÜlikoolNorwegian Biodiversity Information CentreMedical Research Council CanadaDiabetes Research and Wellness FoundationHrvatska Zaklada za ZnanostFondation LeenaardsMagnus Bergvalls StiftelseEmil Aaltosen SäätiöDanish Agency for Science and Higher EducationMarcus och Amalia Wallenbergs minnesfondHögskolan DalarnaInstitut National de la Santé et de la Recherche MédicaleMinistero della SaluteKuopion Yliopistollinen SairaalaNational Institute of Diabetes and Digestive and Kidney DiseasesTurun Yliopistollinen KeskussairaalaKnut och Alice Wallenbergs StiftelseDiabetesliittoNierstichtingMinisterio de Economía y CompetitividadBritish Heart FoundationBundesministerium für Bildung und ForschungMinistero dell’Istruzione, dell’Università e della RicercaErasmus Universiteit RotterdamNational Health and Medical Research CouncilSuomen KulttuurirahastoStrategiske ForskningsrådZonMwNetherlands Heart InstituteDiabetes FondsFondation LeducqEuropean Science FoundationEuropean Regional Development FundKing's College LondonJuvenile Diabetes Research Foundation InternationalCanadian Institutes of Health ResearchDiabetes UKHealthwayHealth and Safety ExecutiveWellcome TrustCancer Research UKNational Institute for Health and Care ResearchAccareDonald W. Reynolds FoundationEli Lilly and CompanyMinistère du Développement Économique, de l’Innovation et de l’ExportationForsknings- og InnovationsstyrelsenFondation de FranceSundhed og Sygdom, Det Frie ForskningsrådGlaxoSmithKlineAmgenErasmus Universitair Medisch Centrum RotterdamLandstinget DalarnasEuropean CommissionJuho Vainion SäätiöAmerican Heart AssociationNational Human Genome Research InstituteDanmarks Frie ForskningsfondInterregAndrea and Charles Bronfman PhilanthropiesJohn D. and Catherine T. MacArthur FoundationNederlandse Organisatie voor Wetenschappelijk OnderzoekBristol-Myers Squibb
KeywordsObesityGeneticsBiologyEnvironmental healthMedicine
Abstract
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Science and technology studies
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.423
Threshold uncertainty score1.000
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 head0.027
GPT teacher head0.232
Teacher spread0.206 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itQuick stats
Citations1
Published2017
Admission routes1
Has abstractyes