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Record W4405828636 · doi:10.17615/bg9g-qs46

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

2024· article· en· W4405828636 on OpenAlexfundno aff
Victor Lim, Donald W. Bowden, Ko Willems van Dijk, Lars Lind, Chad M. Brummett, Iona Y. Millwood, Jian‐Min Yuan, Myung‐Shik Lee, Chiea Chuen Khor, Jie Yao, David U. Gorkin, Jianjun Liu, Alain G. Bertoni, Mark I. McCarthy, Brian E. Cade, Yi‐Jen Hung, Ian Ford, Miguel Cruz, James S. Pankow, Ayo P. Doumatey, Andres Metspalu, Christian Gieger, Jirong Long, Salman M. Tajuddin, Yoonjung Yoonie Joo, Laura J. Rasmussen‐Torvik, James C. Engert, Xiuqing Guo, Mickaël Canouil, Fouad Kandeel, Daniel R. Witte, Robin Walters, Muhammad G. Kibriya, Adán Valladares‐Salgado, Salim Yusuf, Cecilia M. Lindgren, Myron Gross, Kevin Sandow, Liming Li, Daniel Taliun, Jingyi Tan, Jette Bork‐Jensen, Shufa Du, Oscar H. Franco, Mi Yeong Hwang, Harald Grallert, Kent D. Taylor, Charles N. Rotimi, Sina Rüeger, Hasan Shahriar, Jerome I. Rotter, Meng Sun, Dennis O. Mook‐Kanamori, Rob M. van Dam, Chien-Hsiun Chen, Leslie J. Raffel, Xueling Sim, Amel Lamri, Ken Yamamoto, Juliana C.N. Chan, Patricia A. Peyser, Simon Myers, Andrea O. Y. Luk, Bruce M. Psaty, Yang Hai, Sophie Hackinger, Yoichiro Kamatani, Yuan‐Tsong Chen, Fernando Abaitua, Sahoko Ichihara, Timothy M. Frayling, Ching‐Yu Cheng, Kai‐Uwe Eckardt, Oluf Pedersen, Gudmar Thorleifsson, Diane M. Becker, Chloé Sarnowski, Yukinori Okada, Bram P. Prins, Wei‐Min Chen, Gonçalo R. Abecasis, Richard A. Jensen, Kuang Lin, Claudia H. T. Tam, James G. Wilson, Aaron Leong, Robert A. Scott, Varinderpal Kaur, Toshimasa Yamauchi, Jana Nano, Jorge Ferrer, Rohit Varma, Lorena Orozco, Clicerio González‐Villalpando, Sohee Han, Michael Roden, Symen Ligthart, Claudia Schurmann, Zhengming Chen, Marie Loh, Lawrence F. Bielak, Katsuhiko Kohara, Momoko Horikoshi, Dong Mun Shin, Swapan K. Das, Valeriya Lyssenko, Jian’an Luan, Linda S. Adair, Leslie S. Emery, Yongmei Liu, Unnur Thorsteinsdottir, Mary Cushman, Wing Yee So, Sanghoon Moon, Masato Akiyama, Jerry L. Nadler, Michèle M. Sale, Kyong Soo Park, Meraj Ahmad, Dwaipayan Bharadwaj, Edmond K. Kabagambe, Marijana Vujković, Fiona Bragg, Susan Redline, Ivan Brandslund, Rebecca L. Rohde, Jung‐Jin Lee, Mark A. Pereira, Craig L. Hanis, Liang Zhang, M. Geoffrey Hayes, Mart Kals, Daniel Shriner, Ananda R. Wickremasinghe, Soo‐Heon Kwak, Yasuharu Tabara, Jennifer Kriebel, Tomohiro Katsuya, Vilmantas Giedraitis, Abel Kho, Carlos A. Aguilar‐Salinas, Ruifang Li‐Gao, Pauline Genter, Matthias Wuttke, Michele K. Evans, M. Arfan Ikram, Alena Stančáková, Guozhi Jiang, Habibul Ahsan, Michael A. Nalls, Hyeok Sun Choi, Markku Laakso, Jun Lv, Wei Huang, Guanjie Chen, Claudia Langenberg, Charles Kooperberg, Latchezar Dimitrov, Jin Fang Chai, Fumihiko Takeuchi, Jer-Yuarn Wu, Maggie C. Y. Ng, Fuu Jen Tsai, Canqing Yu, Masahiro Nakatochi, Annette Peters, Penny Gordon‐Larsen, Stella Trompet, Tien Yin Wong, Ian Pan, Ching‐Ti Liu, Irene Miguel-Escalada, Valgerður Steinthórsdóttir, Johanna Kuusisto, Nigel W. Rayner, Duk-Hwan Kim, Christian Herder, Nanette R. Lee, Konstantin Strauch, E Shyong Tai, Zheng Bian, Suraj S. Nongmaithem, Xiao-Ou Shu, Girish N. Nadkarni, Eleftheria Zeggini, Guillaume Paré, Anna Köttgen, Myriam Fornage, Roberta McKean‐Cowdin, Andrew P. Morris, Nicholas J. Wareham, Eric A. Whitsel, Ya Xing Wang, Kari E. North, Hidetoshi Kitajima, Michael A. Province, Thomas A. Buchanan, Maike Sander, Danish Saleheen, Laura M. Raffield, Farzana Jasmine, Karen L. Mohlke, Li-Ching Chang, Leif Groop, Yii‐Der Ida Chen, Wei Zheng, John C. Chambers, Chittaranjan S. Yajnik, Kāri Stefánsson, James P. Cook, Kristi Läll, Leo Speidel, Jacob M. Keaton, Annie-Green Howard, Anuradhani Kasturiratne, Mark O. Goodarzi, Alan B. Zonderman, Allan Linneberg, Jinxiu Shi, Masato Isono, Mengna Huang, Ken Suzuki, Krista Fischer, Erwin P. Böttinger, George Dedoussis, Jack U. Flanagan, Chii‐Min Hwu, K. Radha Mani, Xi Luo, Takashi Kadowaki, Qing Duan, Reedik Mägi, Miriam S. Udler, Jason Torres, Gauri Prasad, Lin Tong, Torben Jørgensen, Kyle J. Gaulton, Miao-Li Chee, Pietro Della Briotta Parolo, Juyoung Lee, Philippe Froguel, Michiya Igase, Michael Boehnke, Giriraj R. Chandak, Joshua Chiou, Florian Kronenberg, Lauren E. Petty, Andrew T. Hattersley, Barbara Thorand, Martin Ingelsson, Adrienne M. Stilp, Abbas Dehghan, Simin Liu, Uma Nayak, Ayesha A. Motala, Thomas Meitinger, B. I. Freedman, Jan B. van Klinken, José C. Florez, Fumihiko Matsuda, Lee‐Ming Chuang, Eleanor Wheeler, Sebastian Schönherr, Jaakko Tuomilehto, Ruth J. F. Loos, Aude Nicolas, Charumathi Sabanayagam, Fraser Pirie, Alicia Huerta‐Chagoya, Jennifer E. Below, Shyh‐Huei Chen, Francis S. Collins, Wayne H.-H. Sheu, James B. Meigs, Eli Ipp, Loïc Yengo, Tin Louie, Grace Z. Yu, Takahisa Kawaguchi, María Elena González-Villalpando, Adam E. Locke, Niels Grarup, Bong-Jo Kim, Md. Tariqul Islam, Ping An, Josée Dupuis, Willa A. Hsueh, Adebowale Adeyemo, Ioanna Ntalla, Andrew D. Morris, Darryl Nousome, H. Janaka de Silva, Mitsuhiro Yokota, Christian Fuchsberger, Vasiliki Mamakou, Tamar Sofer, Daniel S. Evans, Shiro Maeda, Sanjay R. Patel, Teresa Tusié‐Luna, Alexander P. Reiner, Lisa R. Yanek, Bianca Porneala, Neil R. Robertson, Raymond Noordam, Mariaelisa Graff, Anna L. Gloyn, Michael Preuß, Marit E. Jørgensen, Sharon L. R. Kardia, Jennifer A. Brody, Kyungheon Yoon, Niels H. Wacher, Leslie A. Lange, Yun Li, Jaspal S. Kooner, Yoon Shin Cho, Ellen M. Schmidt, Jost B. Jonas, Anny H. Xiang, Brian Tomlinson, Sonia S. Anand, Hye-Mi Jang, Norihiro Kato, James S. Floyd, J. Wouter Jukema, Hertzel C. Gerstein, Stephen S. Rich, Cassandra N. Spracklen, Kathryn Roll, Christopher A. Haiman, Sebastian Preißl, R.C.W. Ma, Esteban J. Parra

Bibliographic record

VenueMDC Repository (Max-Delbrueck-Center for Molecular Medicine) · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics, Bioinformatics, and Biomedical Research
Canadian institutionsnot available
FundersShionogiNovo NordiskSanofiKowa CompanyWellcome TrustRespicardiaRegeneron PharmaceuticalsYale UniversityMcMaster UniversityAmgenNational Heart, Lung, and Blood InstitutePfizerAstraZenecaEli Lilly and CompanyGlaxoSmithKline
KeywordsTranslation (biology)Type 2 diabetesComputational biologyEvolutionary biologyGeneticsBiologyGenealogyData scienceDiabetes mellitusComputer scienceHistoryGene

Abstract

fetched live from OpenAlex

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10−9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.287
Threshold uncertainty score0.556

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.039
GPT teacher head0.315
Teacher spread0.276 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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