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Record W2734627099 · doi:10.1038/s41467-017-00031-7

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

2017· review· en· W2734627099 on OpenAlexafffund
M. Carola Zillikens, Serkalem Demissie, Yi-Hsiang Hsu, Laura M. Yerges-Armstrong, Wen‐Chi Chou, Lisette Stolk, Gregory Livshits, Linda Broer, Toby Johnson, Daniel L. Koller, Zoltán Kutalik, Jian’an Luan, Ida Malkin, Janina S. Ried, Albert V. Smith, Guðmar Þorleifsson, Liesbeth Vandenput, Jing Hua Zhao, Weihua Zhang, Ali A. Aghdassi, Kristina Åkesson, Najaf Amin, Leslie J. Baier, Inês Barroso, David A. Bennett, Lars Bertram, Rainer Biffar, Murielle Bochud, Michael Boehnke, Ingrid B. Borecki, Aron S. Buchman, Liisa Byberg, Harry Campbell, Natalia Campos Obanda, Jane A. Cauley, Peggy M. Cawthon, Henna Cederberg, Zhao Chen, Nam H. Cho, Hyung Jin Choi, Melina Claussnitzer, Francis S. Collins, Steven R. Cummings, Philip L. De Jager, Ilja Demuth, R.A.M. Dhonukshe-Rutten, Luda Diatchenko, Guðný Eiríksdóttir, Anke W. Enneman, Mike Erdos, Johan G. Eriksson, Joel Eriksson, Karol Estrada, Daniel S. Evans, Mary F. Feitosa, Mao Fu, Melissa N. Garcia, Christian Gieger, Thomas Girke, Nicole L. Glazer, Harald Grallert, Jagvir Grewal, Bok-Ghee Han, Robert L. Hanson, Caroline Hayward, Albert Hofman, Eric P. Hoffman, Georg Homuth, Wen-Chi Hsueh, Monica J. Hubal, Alan Hubbard, Kim M. Huffman, Lise B. Husted, Thomas Illig, Erik Ingelsson, Till Ittermann, John-Olov Jansson, Joanne M. Jordan, Antti Jula, Magnus K. Karlsson, Kay‐Tee Khaw, Tuomas O. Kilpeläinen, Norman Klopp, Jacqueline S. L. Kloth, Heikki A. Koistinen, William E. Kraus, Stephen B. Kritchevsky, Teemu Kuulasmaa, Johanna Kuusisto, Markku Laakso, Jari Lahti, Thomas Lang, Bente Langdahl, Lenore J. Launer, Jong‐Young Lee, Markus M. Lerch, Joshua R. Lewis, Lars Lind, Cecilia M. Lindgren, Ching‐Ti Liu, Tian Liu, Youfang Liu, Östen Ljunggren, Mattias Lorentzon, Robert Luben, William Maixner, Fiona E. McGuigan, Carolina Medina‐Gómez, Thomas Meitinger, Håkan Melhus, Dan Mellström, Simon Melov, Karl Michaëlsson, Braxton D. Mitchell, Andrew P. Morris, Leif Mosekilde, Anne B. Newman, Carrie M. Nielson, Jeffrey R. O’Connell, Ben A. Oostra, Eric Orwoll, Aarno Palotie, Stephen C.J. Parker, Munro Peacock, Markus Perola, Annette Peters, Ozren Polašek, Richard L. Prince, Katri Räikkönen, Stuart H. Ralston, Samuli Ripatti, John A. Robbins, Jerome I. Rotter, Igor Rudan, Veikko Salomaa, Suzanne Satterfield, Eric E. Schadt, Sabine Schipf, Laura J. Scott, Joban Sehmi, Jian Shen, Chan Soo Shin, Gunnar Sigurðsson, Shad B. Smith, Nicole Soranzo, Alena Stančáková, Elisabeth Steinhagen–Thiessen, Elizabeth A. Streeten, Unnur Styrkársdóttir, Karin M. A. Swart, Sian-Tsung Tan, Mark A. Tarnopolsky, Cynthia A. Thomson, Unnur Þorsteinsdóttir, Emmi Tikkanen, Gregory J. Tranah, Jaakko Tuomilehto, Natasja M. van Schoor, Arjun Verma, Péter Vollenweider, Henry Völzke, Jean Wactawski‐Wende, Mark Walker, Michael N. Weedon, Ryan Welch, H.‐Erich Wichmann, Elisabeth Widén, Frances M. K. Williams, James F. Wilson, Nicole C. Wright, Weijia Xie, Lei Yu, Yanhua Zhou, John C. Chambers, Angela Döring, Cornelia M. van Duijn, Michael J. Econs, Vilmundur Guðnason, Jaspal S. Kooner, Bruce M. Psaty, Timothy D. Spector, Kāri Stefánsson, Fernando Rivadeneira, André G. Uitterlinden, Nicholas J. Wareham, Vicky Ossowski, Dawn Waterworth, Ruth J. F. Loos, David Karasik, Tamara B. Harris, Claes Ohlsson, Douglas P. Kiel

Bibliographic record

VenueNature Communications · 2017
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcMaster University Medical CentreMcGill University
FundersNational Center for Advancing Translational SciencesU.S. National Library of MedicineNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute on AgingMünchner Zentrum für GesundheitswissenschaftenKorea Centers for Disease Control and PreventionNational Health and Medical Research CouncilCanadian Institutes of Health ResearchSchool of Medicine, Johns Hopkins UniversityNational Center for Research ResourcesNational Institute of General Medical SciencesCenters for Disease Control and PreventionNational Institutes of HealthArmy Research OfficeUniversität GreifswaldChinese Society of Clinical OncologyMedical Research CouncilUppsala UniversitetNational Institute of Arthritis and Musculoskeletal and Skin DiseasesGreta och Johan Kocks stiftelserGöteborgs LäkaresällskapSydäntutkimussäätiöAkademiska SjukhusetVetenskapsrådetU.S. Department of Health and Human ServicesGlaxoSmithKlineSigne ja Ane Gyllenbergin SäätiöCentre for Medical Systems BiologyGenome CanadaNovo NordiskFP7 People: Marie-Curie ActionsAmerican Diabetes AssociationVrije Universiteit AmsterdamKaren Elise Jensens FondSvenska LäkaresällskapetDeutsche ForschungsgemeinschaftNederlandse Organisatie voor Wetenschappelijk OnderzoekBritish Heart FoundationBundesministerium für Bildung und ForschungJohns Hopkins UniversityUniversität zu LübeckKing's College LondonAcademy of FinlandMinisterie van Economische Zaken, Landbouw en InnovatieDiabetestutkimussäätiöZonMwSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNederlandse Zuivel OrganisatieErasmus Medisch CentrumMax-Planck-Institut für BildungsforschungStiftelsen för Strategisk ForskningVersus ArthritisHealthwayMalmö HögskolaEuropean Science FoundationNational Human Genome Research InstituteDanmarks Frie ForskningsfondKidney Research UKRoyal SocietyNational Institute for Health and Care ResearchWageningen University and ResearchCancer Research UKWellcome TrustNational Heart, Lung, and Blood InstituteItä-Suomen YliopistoFoundation for Cardiovascular ResearchFinska LäkaresällskapetYrjö Jahnssonin SäätiöAstraZenecaEuropean CommissionHelsingin YliopistoSchool of Medicine, Boston UniversityChronic Disease Research FoundationKuopion Yliopistollinen SairaalaWake Forest UniversityScottish GovernmentHjartaverndIllinois Department of Public HealthCedars-Sinai Medical CenterMinistry of Cultural AffairsEmil Aaltosen SäätiöNational Science FoundationJuho Vainion SäätiöNovo Nordisk FondenAmerican Heart Association
KeywordsGenome-wide association studyGeneticsBiologyGenomeComputational biologyMeta-analysisAssociation (psychology)MedicineGeneGenotypeSingle-nucleotide polymorphismPsychology

Abstract

fetched live from OpenAlex

Abstract Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass ( n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide ( p < 5 × 10 −8 ) or suggestively genome wide ( p < 2.3 × 10 −6 ). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3 , IRS1 , and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN , ADAMTSL3 , and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.

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 distilled prediction

Teacher imitation

Not 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)0.002
metaresearch head score (Gemma)0.010
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.694
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.010
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.004
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.159
GPT teacher head0.449
Teacher spread0.290 · 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 teacher head, not a consensus.

Study designMeta-analysis
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

Citations187
Published2017
Admission routes2
Has abstractyes

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