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Record W2729907866 · doi:10.1038/ncomms16015

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

2017· article· en· W2729907866 on OpenAlexaff
Sara M. Willems, Daniel J. Wright, Felix R. Day, Katerina Trajanoska, Peter K. Joshi, John Morris, Amy M. Matteini, Fleur C. Garton, Niels Grarup, Nikolay Oskolkov, Anbupalam Thalamuthu, Massimo Mangino, Jun Liu, Ayşe Demirkan, Monkol Lek, Li‐Wen Xu, Guan Wang, Christopher Oldmeadow, Kyle J. Gaulton, Luca A. Lotta, Eri Miyamoto‐Mikami, Manuel A. Rivas, Tom White, Po‐Ru Loh, Mette Aadahl, Najaf Amin, John Attia, Krista G. Austin, Beben Benyamin, Søren Brage, Yu‐Ching Cheng, Paweł Cięszczyk, Wim Derave, Karl‐Fredrik Eriksson, Nir Eynon, Allan Linneberg, Alejandro Lucía, Myosotis Massidda, Braxton D. Mitchell, Motohiko Miyachi, Haruka Murakami, Sandosh Padmanabhan, Ashutosh K. Pandey, Ioannis Papadimitriou, Deepak K. Rajpal, Craig Sale, Theresia M. Schnurr, Francesco Sessa, Nick Shrine, Martin D. Tobin, Ian Varley, Louise V. Wain, Naomi R. Wray, Cecilia M. Lindgren, Daniel G. MacArthur, Dawn Waterworth, Mark I. McCarthy, Oluf Pedersen, Kay‐Tee Khaw, Douglas P. Kiel, Ling Oei, Hou-Feng Zheng, Vincenzo Forgetta, Aaron Leong, Omar Ahmad, Charles Laurin, Lauren E. Mokry, Stephanie Ross, Cathy E. Elks, Jack Bowden, Nicole M. Warrington, Anna Murray, Katherine S. Ruth, Konstantinos K. Tsilidis, Carolina Medina‐Gómez, Karol Estrada, Joshua C. Bis, Daniel I. Chasman, Serkalem Demissie, Anke W. Enneman, Yi‐Hsiang Hsu, Þorvaldur Ingvarsson, Mika Kähönen, Candace M. Kammerer, Andrea Z. LaCroix, Li Guo, Ching‐Ti Liu, Mattias Lorentzon, Reedik Mägi, Evelin Mihailov, Lili Milani, Alireza Moayyeri, Carrie M. Nielson, Pack Chung Sham, Kristin Siggeirsdotir, Gunnar Sigurðsson, Kāri Stefánsson, Stella Trompet, Guðmar Þorleifsson, Liesbeth Vandenput, Nathalie van der Velde, Jorma Viikari, Su‐Mei Xiao, Wei Zhao, Daniel S. Evans, Steven R. Cummings, Jane A. Cauley, Emma L. Duncan, C.P.G.M. de Groot, Tõnu Esko, Tamara B. Harris, Rebecca D. Jackson, J. Wouter Jukema, Arfan M. Ikram, David Karasik, Stephen Kaptoge, A W Kung, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Paul Lips, Robert Luben, Andres Metspalu, Joyce B. J. van Meurs, Ryan L. Minster, Erick Orwoll, Edwin H. G. Oei, Bruce M. Psaty, Olli T. Raitakari, Stuart W. Ralston, Paul M. Ridker, John A. Robbins, Albert V. Smith, Unnur Styrkársdóttir, Gregory J. Tranah, Unnur Thorstensdottir, André G. Uitterlinden, Joseph M. Zmuda, M. Carola Zillikens, Evangelia Ntzani, Εvangelos Εvangelou, John P. A. Ioannidis, David M. Evans, Claes Ohlsson, Yannis Pitsiladis, Noriyuki Fuku, Paul W. Franks, Kathryn N. North, Cornelia M. van Duijn, Karen A. Mather, Torben Hansen, Ola Hansson, Tim D. Spector, Joanne M. Murabito, J. Brent Richards, Fernando Rivadeneira, Claudia Langenberg, John R. B. Perry, Robert A. Scott

Bibliographic record

VenueNature Communications · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Physical Performance
Canadian institutionsMcGill UniversityMcMaster UniversityJewish General Hospital
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institute of Arthritis and Musculoskeletal and Skin DiseasesMedical Research CouncilNational Institutes of HealthJapan Society for the Promotion of ScienceNational Health and Medical Research CouncilCancer Research UKNovo Nordisk FondenCopenhagen Graduate School for Nanoscience and NanotechnologyNovo Nordisk Foundation Center for Basic Metabolic ResearchNational Institute for Health and Care ResearchNovo NordiskNational Institute on AgingMinistry of Education, Culture, Sports, Science and TechnologyEuropean CommissionKing's College LondonNIH Clinical CenterU.S. Department of Veterans AffairsLundbeckfondenNational Center for Advancing Translational SciencesNational Human Genome Research InstituteWellcome Trust
KeywordsGenome-wide association studyScale (ratio)Computer scienceComputational biologyBiologyGeneticsSingle-nucleotide polymorphismGeographyGeneCartography

Abstract

fetched live from OpenAlex

Abstract Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength ( P <5 × 10 −8 ) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres ( ACTG1 ), neuronal maintenance and signal transduction ( PEX14, TGFA, SYT1 ), or monogenic syndromes with involvement of psychomotor impairment ( PEX14, LRPPRC and KANSL1 ). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

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)0.001
metaresearch head score (Gemma)0.002
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 score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
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 head0.023
GPT teacher head0.309
Teacher spread0.286 · 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".

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Citations229
Published2017
Admission routes1
Has abstractyes

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