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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
Paul S. de Vries, Michael R. Brown, Amy R. Bentley, Thomas W Winkler, Ιωάννα Ντάλλα, Karen Schwander, Aldi T. Kraja, Xiuqing Guo, Nora Franceschini, Ching‐Yu Cheng, Xueling Sim, Dina Vojinović, Jennifer E. Huffman, Solomon K. Musani, Changwei Li, Mary F. Feitosa, Melissa A. Richard, Raymond Noordam, Hugues Aschard, Traci M. Bartz, Lawrence F. Bielak, Xuan Deng, Rajkumar Dorajoo, Kurt K. Lohman, Tuomo Rankinen, Albert V. Smith, Salman M. Tajuddin, Εvangelos Εvangelou, Mariaelisa Graff, Maris Alver, Mathilde Boissel, Jin Fang Chai, Xu Chen, Jasmin Divers, Ilaria Gandin, Chuan Gao, Anuj Goel, Yanick Hagemeijer, Sarah E. Harris, Fernando Pires Hartwig, Meian He, Andréa R. V. R. Horimoto, Fang‐Chi Hsu, Anne Jackson, Anuradhani Kasturiratne, Pirjo Komulainen, Brigitte Kühnel, Federica Laguzzi, Joseph H. Lee, Jian’an Luan, Leo‐Pekka Lyytikäinen, Nana Matoba, Ilja M. Nolte, Maik Pietzner, Muhammad Riaz, M. Abdullah Said, Robert A. Scott, Tamar Sofer, Alena Stančáková, Fumihiko Takeuchi, Bamidele O. Tayo, Peter J. van der Most, Tibor V. Varga, Yajuan Wang, Erin B. Ware, Wanqing Wen, Lisa R. Yanek, Weihua Zhang, Jing Hua Zhao, Saima Afaq, Najaf Amin, Marzyeh Amini, Dan E. Arking, Tin Aung, Christie M. Ballantyne, Eric Boerwinkle, Ulrich Broeckel, Archie Campbell, Mickaël Canouil, Charumathi Sabanayagam, Yii‐Der Ida Chen, John Connell, Ulf dé Fairé, Lisa de las Fuentes, Renée de Mutsert, H Janaka de Silva, Jingzhong Ding, Anna F. Dominiczak, Qing Duan, Charles B. Eaton, Ruben N. Eppinga, Jessica D. Faul, Virginia Fisher, Terrence Forrester, Oscar H. Franco, Yechiel Friedlander, Mohsen Ghanbari, Franco Giulianini, Hans J. Grabe, Megan L. Grove, C. Charles Gu, Tamara B. Harris, Sami Heikkinen, Chew‐Kiat Heng, Makoto Hirata, James E. Hixson, Barbara V. Howard, M. Arfan Ikram, David R. Jacobs, Craig Johnson, Jost B. Jonas, Candace M. Kammerer, Tomohiro Katsuya, Chiea Chuen Khor, Tuomas O. Kilpeläinen, Woon‐Puay Koh, Heikki A. Koistinen, Ivana Kolčić, Charles Kooperberg, José Eduardo Krieger, Steve Kritchevsky, Michiaki Kubo, Johanna Kuusisto, Timo A Lakka, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Benjamin Lehne, Rozenn N. Lemaître, Yize Li, Jingjing Liang, Jianjun Liu, Kiang Liu, Marie Loh, Tin Louie, Reedik Mägi, Ani Manichaikul, Colin A. McKenzie, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Lili Milani, Karen L. Mohlke, Thomas H. Mosley, Kenneth J. Mukamal, Mike A. Nalls, Matthias Nauck, Christopher P. Nelson, Nona Sotoodehnia, Jeff O’Connell, Raha Pazoki, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Ozren Polašek, Neil Poulter, Leslie J. Raffel, Olli Raitakari, Alex P. Reiner, Treva Rice, Stephen S. Rich, Antonietta Robino, Jennifer G. Robinson, Lynda M. Rose, Igor Rudan, Carsten Oliver Schmidt, Pamela J. Schreiner, William R. Scott, Peter Sever, Yuan Shi, Stephen Sidney, Mario Sims, Blair H. Smith, Jennifer A. Smith, Harold Snieder, John M. Starr, Konstantin Strauch, Nicholas Y.Q. Tan, Kent D. Taylor, Yik Ying Teo, Yih Chung Tham, André G. Uitterlinden, Dragana Vuckovic, Mélanie Waldenberger, Lihua Wang, Yujie Wang, Zhe Wang, Wen Bin Wei, Christine A. Williams, Gregory Wilson, Mary K. Wojczynski, Jie Yao, Bing Yu, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Alan B Zonderman, Diane M. Becker, Michael Boehnke, Donald W. Bowden, John C. Chambers, Ian J. Deary, Tõnu Esko, Martin Farrall, Paul W. Franks, Barry I. Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Bernardo Lessa Horta, Norihiro Kato, Jaspal S. Kooner, Markku Laakso, Karin Leander, Terho Lehtimäki, Patrik K. E. Magnusson, Brenda W.J.H. Penninx, Alexandre C. Pereira, Rainer Rauramaa, Nilesh J Samani, James G. Scott, Xiao‐Ou Shu, Pim van der Harst, Lynne E. Wagenknecht, Ya Xing Wang, Nicholas J. Wareham, Hugh Watkins, David R. Weir, Ananda R. Wickremasinghe, Wei Zheng, Paul Elliott, Kari E. North, Claude Bouchard, Michele K. Evans, Vilmundur Guðnason, Ching‐Ti Liu, Bruce M. Psaty, Paul M. Ridker, Rob M. van Dam, Sharon L. R. Kardia, Xiaofeng Zhu, Charles Rotimi, Dennis O. Mook‐Kanamori, Myriam Fornage, Tanika N. Kelly, Ervin R. Fox, Caroline Hayward, Cornelia M. van Duijn, E Shyong Tai, Tien Yin Wong, Jingmin Liu, Jerome I. Rotter, W. James Gauderman, Michael A. Province, Patricia B. Munroe, Kenneth Rice, Daniel I. Chasman, L Adrienne Cupples, D. C. Rao, Alanna C. Morrison
Bibliographic record
VenueAmerican Journal of Epidemiology · 2019
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersSociale en Geesteswetenschappen, NWOCore Research for Evolutional Science and TechnologyFondo Nacional de Desarrollo Científico y TecnológicoInstitute of GeneticsSchool of Medicine, University of California, IrvineSchool of Medicine, University of North Carolina at Chapel HillNational Institute on Minority Health and Health DisparitiesNational Center on Minority Health and Health DisparitiesCenter for Information TechnologyNational Institute of Dental and Craniofacial ResearchNational Cancer InstituteNational Eye InstituteNIH Office of the DirectorNational Institute on AgingNIHR Barts Biomedical Research Centre, Queen Mary University of LondonFaculty of Medicine and Health, University of SydneyNIHR Leicester Biomedical Research CentreInstitute of Medical Science, University of TokyoSchool of Public Health, Imperial College LondonTongji Medical College, Huazhong University of Science and TechnologyNational Key Research and Development Program of ChinaMedicinska fakulteten, Umeå UniversitetRIKENProgram for New Century Excellent Talents in UniversityFaculty of Science, National University of SingaporeEuropean Research CouncilBiotechnology and Biological Sciences Research CouncilFifth Framework ProgrammeUniversité de LilleSixth Framework ProgrammeUniversity of California, IrvineGraduate School of Public Health, University of PittsburghDirectorate for Biological SciencesNational University of SingaporeNational Institutes of HealthAction on Hearing LossAmsterdam NeuroscienceNational Institute of Diabetes and Digestive and Kidney DiseasesSan Diego State UniversityKaiser Foundation Research InstituteMedStar Health Research InstituteUK Dementia Research InstituteKelaTerveyden ja hyvinvoinnin laitosHuazhong University of Science and TechnologyNovo Nordisk Foundation Center for Basic Metabolic ResearchNational University Health SystemAmgenUniversity of KelaniyaHouston Methodist Research InstituteCentre Hospitalier Universitaire de RennesU.S. Environmental Protection AgencySkånes universitetssjukhusFakultet Medicinskih Nauka, Univerziteta U KragujevcuDiabetesliittoTampereen TuberkuloosisäätiöForskningsrådet om Hälsa, Arbetsliv och VälfärdEuropean CommissionUniversity of North Carolina at Chapel HillMinistério da EducaçãoNational Institute of Neurological Disorders and StrokePaavo Nurmen SäätiöMinisterie van Economische ZakenTechnische Universität MünchenUniversidade de São PauloGenome Institute of SingaporeUniversity of MiamiGeorgetown UniversitySydäntutkimussäätiöUniversitair Medisch Centrum GroningenUmeå UniversitetMinistério da SaúdeBarts and The London School of Medicine and DentistryEmil Aaltosen SäätiöServierMinistry of Economic AffairsStockholms Läns LandstingUniversity of AlabamaAssociação Brasileira de Saúde ColetivaNational Center for Advancing Translational SciencesPäivikki ja Sakari Sohlbergin SäätiöUniversity of Southern CaliforniaKuopion Yliopistollinen SairaalaJuho Vainion SäätiöCentre for Cognitive Ageing and Cognitive EpidemiologyMedical Research CouncilHjärt-LungfondenNovo NordiskHebrew University of JerusalemHjartaverndJackson State UniversityTekesItä-Suomen YliopistoSouthern California Clinical and Translational Science InstituteFaculty of Health and Medical Sciences, University of Western AustraliaLunds UniversitetChief Scientist Office, Scottish Government Health and Social Care DirectorateMinistero della SaluteWake Forest School of MedicineNational Human Genome Research InstituteJapan Science and Technology AgencyMRC-PHE Centre for Environment and HealthFundação de Amparo à Pesquisa do Estado de São PauloFondation de FranceJapan Agency for Medical Research and DevelopmentSigne ja Ane Gyllenbergin SäätiöFédération Française de CardiologieU.S. National Library of MedicineCenter for Clinical and Translational Sciences, University of Texas Health Science Center at HoustonErasmus Medisch CentrumLoyola University Chicago Stritch School of MedicineTurun Yliopistollinen KeskussairaalaCapital Medical UniversityUniversität HeidelbergBundesministerium für Bildung und ForschungAcademy of FinlandCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorRussian Foundation for Basic ResearchSchool of Medicine, University of MarylandUniversity of Alabama at BirminghamImperial College LondonPublic Health EnglandFoundation for Cardiovascular ResearchZonMwStiftelsen för Strategisk ForskningInstitut National de la Santé et de la Recherche MédicaleCentre for Medical Systems BiologyWashington University in St. LouisMinerva FoundationEnvironmental Protection AgencyNational Institute on Deafness and Other Communication DisordersAgency for Science, Technology and ResearchRoy J. and Lucille A. Carver College of Medicine, University of IowaNorthwestern UniversityUniversity of WashingtonUniversity of BristolSanofiUniversity of OxfordUniversity of LeicesterBrown UniversityKidney Research UKNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Research Foundation SingaporeErasmus Universitair Medisch Centrum RotterdamBritish Heart FoundationEesti TeadusagentuurOffice of Dietary SupplementsNational Research FoundationDiabetes FondsNational Science Foundation, United Arab EmiratesNational Institute for Health and Care ResearchUniversidade Federal de PelotasSchool of Medicine, University of VirginiaUniversity of GlasgowTopcon CorporationDuke-NUS Medical SchoolBrigham and Women's HospitalTulane UniversityLes Laboratories Pierre FabreScottish GovernmentEuropean Regional Development FundKarolinska InstitutetSchool of Public Health, University of MichiganPfizerImperial College Healthcare NHS TrustUniversität GreifswaldScottish Government Health and Social Care DirectorateDiabetes Research CenterNational Institute of Nursing ResearchUniversiteit LeidenHankuk University of Foreign StudiesWake Forest UniversityHadassah Medical OrganizationHome OfficeUniversity of DundeeJohns Hopkins UniversityWellcome TrustNational Natural Science Foundation of ChinaLee Kong Chian School of Medicine, Nanyang Technological UniversitySchool of Medicine, Boston UniversityYrjö Jahnssonin SäätiöHarvard UniversityDepartment of Science and Technology, PhilippinesIntramural Research ProgramQueen Mary University of LondonUniversity of PittsburghUniversity of BernCancer Research UKVetenskapsrådetScottish Funding CouncilMinistry of Education, Culture, Sports, Science and TechnologyHelsingin ja Uudenmaan SairaanhoitopiiriWorld Health OrganizationDet Sundhedsvidenskabelige Fakultet, Københavns UniversitetKaiser PermanenteMashhad University of Medical SciencesMassachusetts Institute of TechnologyNovartis Pharmaceuticals CorporationNational Center for Research ResourcesInternational Development Research CentreNational Center for Global Health and MedicineNational Institute for Health Research Health Protection Research UnitCentre National de la Recherche ScientifiqueRijksuniversiteit GroningenNational Medical Research CouncilSuomen KulttuurirahastoAmerican Heart AssociationSchool of Medicine, Vanderbilt UniversityCase Western Reserve UniversitySchool of Medicine, Johns Hopkins UniversityUniversity of MinnesotaWellcomeSchool of Medicine, Case Western Reserve UniversityMinistry of Cultural AffairsBroad InstituteLeids Universitair Medisch CentrumHelmholtz Zentrum MünchenHelsingin YliopistoTorsten Söderbergs StiftelseHrvatska Zaklada za ZnanostAge UKFoundation for the National Institutes of HealthMinistry of Education and ScienceNanyang Technological UniversitySociété Francophone du DiabèteNational Institute of Biomedical InnovationEli Lilly and CompanySiemensNierstichtingTongji UniversityAssociation Diabète Risque VasculaireUniversity of EdinburghKnut och Alice Wallenbergs StiftelseBiomedical Research CouncilSeventh Framework ProgrammeNational Heart, Lung, and Blood InstituteAstraZenecaWomen's Health InitiativeVanderbilt UniversityFeinberg School of MedicineTurun YliopistoYale UniversityLoyola University Chicago
KeywordsGenome-wide association studyGeneGeneticsAlcoholBiologyGenetic associationComputational biologyMedicineGenotypeSingle-nucleotide polymorphismBiochemistry
Abstract
A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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)0.005
metaresearch head score (Gemma)0.007
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: Review · Consensus signal: none
Teacher disagreement score0.007
Threshold uncertainty score0.026
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 head0.104
GPT teacher head0.400
Teacher spread0.297 · 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 itClassification
machine, unvalidatedMachine 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
GenreReview
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
Citations141
Published2019
Admission routes1
Has abstractyes