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Record W2148749248 · doi:10.1038/ng.2897

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

2014· review· en· W2148749248 on OpenAlexafffund
Anubha Mahajan, Min Jin Go, Weihua Zhang, Jennifer E. Below, Kyle J. Gaulton, Teresa Ferreira, Momoko Horikoshi, Andrew D. Johnson, Maggie C. Y. Ng, Inga Prokopenko, Danish Saleheen, Xu Wang, Eleftheria Zeggini, Gonçalo R. Abecasis, Linda S. Adair, Peter Almgren, Mustafa Atalay, Tin Aung, Damiano Baldassarre, Beverley Balkau, Yuqian Bao, Anthony Barnett, Inês Barroso, Abdul Basit, Latonya Been, John Beilby, Graeme I. Bell, Rafn Benediktsson, Richard N. Bergman, Bernhard O. Boehm, Eric Boerwinkle, Lori L. Bonnycastle, Noël P. Burtt, Qiuyin Cai, Harry Campbell, Jason Carey, Stéphane Cauchi, Mark J. Caulfield, Juliana C.N. Chan, Li-Ching Chang, Tien‐Jyun Chang, Yi‐Cheng Chang, G. Charpentier, Chien-Hsiun Chen, Han Chen, Yuan-Tsong Chen, Kee‐Seng Chia, Manickam Chidambaram, Peter S. Chines, Nam H. Cho, Young Min Cho, Lee‐Ming Chuang, Francis S. Collins, Marilyn C. Cornelis, David Couper, Andrew Crenshaw, Rob M. van Dam, John Danesh, Debashish Das, Ulf dé Fairé, George Dedoussis, Panos Deloukas, Antigone S. Dimas, Christian Dina, Alex S. F. Doney, Peter Donnelly, Mozhgan Dorkhan, Cornelia M. van Duijn, Josée Dupuis, Sarah Edkins, Paul Elliott, Valur Emilsson, Raimund Erbel, Johan G. Eriksson, Jorge Escobedo, Tõnu Esko, Elodie Eury, José C. Florez, Pierre Fontanillas, Nita G. Forouhi, Tom Forsén, Caroline S. Fox, Ross M. Fraser, Timothy M. Frayling, Philippe Froguel, Philippe Frossard, Yu‐Tang Gao, Karl Gertow, Christian Gieger, Bruna Gigante, Harald Grallert, George Grant, Leif Groop, Christopher J. Groves, Elin Grundberg, Candace Guiducci, Anders Hamsten, Bok‐Ghee Han, Kazuo Hara, Neelam Hassanali, Andrew T. Hattersley, Caroline Hayward, Åsa K. Hedman, Christian Herder, Albert Hofman, Oddgeir L. Holmen, Kees Hovingh, Ástráður B. Hreiðarsson, Cheng Hu, Frank B. Hu, Jennie Hui, Steve E. Humphries, Sarah Hunt, David J. Hunter, Kristian Hveem, Muhammad Zafar Iqbal Hydrie, Hiroshi Ikegami, Thomas Illig, Erik Ingelsson, Muhammed Islam, Bo Isomaa, Anne Jackson, Tazeen Jafar, Weiping Jia, Karl‐Heinz Jöckel, Anna Jonsson, Jeremy B. M. Jowett, Takashi Kadowaki, Hyun Min Kang, Stavroula Kanoni, Wen Hong Linda Kao, Sekar Kathiresan, Norihiro Kato, Prasad Katulanda, Sirkka Keinänen‐Kiukaanniemi, Ann M Kelly, Hassan Khan, Kay‐Tee Khaw, Chiea Chuen Khor, Hyung-Lae Kim, Sang Soo Kim, Young Jin Kim, Leena Kinnunen, Norman Klopp, Augustine Kong, Eeva Korpi-Hyövälti, Sudhir Kowlessur, Peter Kraft, Jasmina Kravić, Malene M. Kristensen, S. Krithika, Ashish Kumar, J Kumate, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Vasiliki Lagou, Timo A. Lakka, Claudia Langenberg, Cordelia Langford, Robert Lawrence, Karin Leander, Jen-Mai Lee, Sang Lee, Man Li, Yun Li, Junbin Liang, Samuel Liju, Wei‐Yen Lim, Lars Lind, Cecilia M. Lindgren, Eero Lindholm, Ching‐Ti Liu, Jianjun Liu, Stéphane Lobbens, Jirong Long, Ruth J. F. Loos, Wei Lu, Jian’an Luan, Valeriya Lyssenko, Ronald C.W., Shiro Maeda, Reedik Mägi, Satu Männistö, David R Matthews, James B. Meigs, Olle Melander, Andres Metspalu, Julia Meyer, Ghazala Mirza, Evelin Mihailov, Susanne Moebus, Viswanathan Mohan, Karen L. Mohlke, Andrew D. Morris, Martina Müller‐Nurasyid, Bill Musk, Jiro Nakamura, Eitaro Nakashima, Pau Navarro, Peng-Keat Ng, Alexandra C. Nica, Peter M. Nilsson, Inger Njølstad, Markus M. Nöthen, Keizo Ohnaka, Twee Hee Ong, Katharine R. Owen, James S. Pankow, Kyong Soo Park, Melissa Parkin, Sonali Pechlivanis, Nancy L. Pedersen, Leena Peltonen, John R. B. Perry, Annette Peters, Janani Pinidiyapathirage, Carl Platou, Simon Potter, Jackie F. Price, Lu Qi, Venkatesan Radha, Lοukianos S. Rallidis, Asif Rasheed, Wolfgang Rathmann, Rainer Rauramaa, Soumya Raychaudhuri, Nigel W. Rayner, Simon D. Rees, Emil Rehnberg, Samuli Ripatti, Neil Robertson, Michael Roden, Elizabeth J. Rossin, Igor Rudan, Denis Rybin, Timo Saaristo, Veikko Salomaa, Juha Saltevo, Maria Samuel, Dharambir K. Sanghera, Jouko Saramies, James Scott, Laura J. Scott, Robert A. Scott, Ayellet V. Segrè, Joban Sehmi, Bengt Sennblad, Nabi Shah, Sonia Shah, A. Samad Shera, Xiao Ou Shu, Alan R. Shuldiner, Gunnar Sigurðsson, Eric J.G. Sijbrands, Angela Silveira, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S. Small, Wing Yee So, Alena Stančáková, Kāri Stefánsson, Gerald Steinbach, Valgerður Steinthórsdóttir, Kathleen Stirrups, Rona J. Strawbridge, Heather M. Stringham, Qi Sun, Chen Suo, Ann‐Christine Syvänen, Ryoichi Takayanagi, Fumihiko Takeuchi, Wan Ting Tay, Tanya M. Teslovich, Barbara Thorand, Guðmar Þorleifsson, Unnur Þorsteinsdóttir, Emmi Tikkanen, Joseph Trakalo, Elena Tremoli, Mieke D. Trip, Fuu Jen Tsai, Jaakko Tuomilehto, André G. Uitterlinden, Adán Valladares‐Salgado, Sailaja Vedantam, Fabrizio Veglia, Benjamin F. Voight, Congrong Wang, Nicholas J. Wareham, Roman Wennauer, Ananda R. Wickremasinghe, Tom Wilsgaard, James F. Wilson, Steven Wiltshire, Wendy Winckler, Tien Yin Wong, Andrew R. Wood, Jer‐Yuarn Wu, Ying Wu, Ken Yamamoto, Toshimasa Yamauchi, Ming‐Yu Yang, Loïc Yengo, Mitsuhiro Yokota, Robin Young, Delilah Zabaneh, Fan Zhang, Rong Zhang, Wei Zheng, Paul Zimmet, David Altshuler, Donald W. Bowden, Yoon Shin Cho, Nancy J. Cox, Miguel Cruz, Craig L. Hanis, Jaspal S. Kooner, Jong‐Young Lee, Mark Seielstad, Yik Ying Teo, Michael Boehnke, Esteban J. Parra, John C. Chambers, E Shyong Tai, Mark I. McCarthy, Andrew P. Morris

Bibliographic record

VenueNature Genetics · 2014
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity of Toronto
FundersFP7 HealthNational Institute of Diabetes and Digestive and Kidney DiseasesInstituto de Seguriidad y Servicios Sociales de los Trabadores del EstadoMedical Research CouncilNovo Nordisk FondenInstituto Mexicano del Seguro SocialEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEuropean CommissionCanadian Institutes of Health ResearchNational Institute of General Medical SciencesNational Institute for Health and Care ResearchNational Institutes of HealthNational Center for Advancing Translational SciencesNational Human Genome Research InstituteWellcome TrustConsejo Nacional de Ciencia y TecnologíaBritish Heart Foundation
KeywordsGenome-wide association studyBiologyGenetic architectureGeneticsGenetic associationSingle-nucleotide polymorphismGenetic genealogyAlleleType 2 diabetes1000 Genomes ProjectMeta-analysisEvolutionary biologyQuantitative trait locusGeneGenotypeDiabetes mellitusPopulationMedicineEnvironmental health

Abstract

fetched live from OpenAlex

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations. To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

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)0.003
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.003
Threshold uncertainty score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.000

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 head0.033
GPT teacher head0.317
Teacher spread0.285 · 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 designMeta-analysis
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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Citations1,079
Published2014
Admission routes2
Has abstractno

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