Record W3044478263 · doi:10.1101/2020.07.23.217646

The Trans-Ancestral Genomic Architecture of Glycaemic Traits

2020· preprint· en· W3044478263 on OpenAlexaff

Ji Chen, Cassandra N. Spracklen, Gaëlle Marenne, Arushi Varshney, Laura J. Corbin, Jian’an Luan, Sara M. Willems, Ying Wu, Xiaoshuai Zhang, Momoko Horikoshi, Thibaud Boutin, Reedik Mägi, Johannes Waage, Achilleas Pitsilides, Ruifang Li‐Gao, Kei Hang, Jie Yao, Mila Desi Anasanti, Audrey Y. Chu, Annique Claringbould, Jani Heikkinen, Jaeyoung Hong, Jouke‐Jan Hottenga, Shaofeng Huo, Marika Kaakinen, Tin Louie, Winfried März, Hortensia Moreno-Macías, Anne Ndungu, Sarah C. Nelson, Ilja M. Nolte, Kari E. North, Chelsea K. Raulerson, Debashree Ray, Rebecca Rohde, Denis Rybin, Claudia Schurmann, Xueling Sim, Loz Southam, Isobel D. Stewart, Carol A. Wang, Yujie Wang, Peitao Wu, Weihua Zhang, Tarunveer S. Ahluwalia, Emil VR Appel, Lawrence F. Bielak, Jennifer A. Brody, Noël P. Burtt, Claudia Cabrera, Brian E. Cade, Jin Fang Chai, Xiaoran Chai, Li-Ching Chang, Chien-Hsiun Chen, Brian H. Chen, Kumaraswamy Naidu Chitrala, Yen‐Feng Chiu, Hugoline G. de Haan, Graciela E. Delgado, Ayşe Demirkan, Qing Duan, Jorgen Engmann, Segun Fatumo, Javier Gayán, Franco Giulianini, Jung Ho Gong, Stefan Gustafsson, Yang Hai, Fernando Pires Hartwig, Jing He, Yoriko Heianza, Tao Huang, Alicia Huerta‐Chagoya, Mi Yeong Hwang, Richard A. Jensen, Takahisa Kawaguchi, Katherine A. Kentistou, Young Jin Kim, Marcus E. Kleber, Ishminder K. Kooner, Shuiqing Lai, Leslie A. Lange, Carl D. Langefeld, Marie Lauzon, Man Li, Symen Ligthart, Jun Liu, Marie Loh, Jirong Long, Valeriya Lyssenko, Massimo Mangino, Carola Marzi, May E. Montasser, Abhishek Nag, Masahiro Nakatochi, Damia Noce, Raymond Noordam, Giorgio Pistis, Michael Preuß, Laura M. Raffield, Laura J. Rasmussen‐Torvik, Stephen S. Rich, Neil R. Robertson, Rico Rueedi, Kathleen A. Ryan, Serena Sanna, Richa Saxena, Katharina E. Schraut, Bengt Sennblad, Kazuya Setoh, Albert V. Smith, Lorraine Southam, Thomas Sparsø, Rona J. Strawbridge, Fumihiko Takeuchi, Jingyi Tan, Stella Trompet, Erik B. van den Akker, Peter J. van der Most, Niek Verweij, Mandy Vogel, Heming Wang, Chaolong Wang, Nan Wang, Helen R. Warren, Wanqing Wen, Tom Wilsgaard, Andrew Wong, Andrew R. Wood, Tian Xie, Mohammad Hadi Zafarmand, Jinghua Zhao, Wei Zhao, Najaf Amin, Zorayr Arzumanyan, Arne Astrup, Stephan J. L. Bakker, Damiano Baldassarre, Marian Beekman, Richard N. Bergman, Alain G. Bertoni, Matthias Blüher, Lori L. Bonnycastle, Stefan R. Bornstein, Donald W. Bowden, Qiuyin Cai, Archie Campbell, Harry Campbell, Yi‐Cheng Chang, Eco J. C. de Geus, Abbas Dehghan, Shufa Du, Guðný Eiríksdóttir, Aliki Eleni Farmaki, Mattias Frånberg, Christian Fuchsberger, Yu‐Tang Gao, Anette P. Gjesing, Anuj Goel, Sohee Han, Catharina A. Hartman, Christian Herder, Andrew A. Hicks, Chang‐Hsun Hsieh, Willa A. Hsueh, Sahoko Ichihara, Michiya Igase, M. Arfan Ikram, W. Craig Johnson, Marit E. Jørgensen, Peter K. Joshi, Rita R. Kalyani, Fouad Kandeel, Tomohiro Katsuya, Chiea Chuen Khor, Wieland Kieß, Ivana Kolčić, Teemu Kuulasmaa, Johanna Kuusisto, Kristi Läll, Kelvin Lam, Sang Lee, Rozenn N. Lemaître, Honglan Li, Lifelines Cohort Study, Shih-Yi Lin, Jaana Lindström, Allan Linneberg, Jianjun Liu, Carlos Lorenzo, Tatsuaki Matsubara, Fumihiko Matsuda, Geltrude Mingrone, Simon P. Mooijaart, Sanghoon Moon, Toru Nabika, Girish N. Nadkarni, Jerry L. Nadler, Mari Nelis, Matthew Neville, Jill M. Norris, Yasumasa Ohyagi, Annette Peters, Patricia A. Peyser, Ozren Polašek, Qibin Qi, Dennis Raven, Dermot F. Reilly, Alex P. Reiner, Fernando Rivideneira, Kathryn Roll, Igor Rudan, Charumathi Sabanayagam, Kevin Sandow, Naveed Sattar, Annette Schürmann, Jinxiu Shi, Heather M. Stringham, Kent D. Taylor, Tanya M. Teslovich, Betina H. Thuesen, Paul R. H. J. Timmers, Elena Tremoli, Michael Y. Tsai, André G. Uitterlinden, Rob M. van Dam, Astrid van Hylckama Vlieg, Jana V. van Vliet‐Ostaptchouk, Jagadish Vangipurapu, Henrik Vestergaard, Tao Wang, Ko Willems van Dijk, Yong‐Bing Xiang, Tatijana Zemunik, Gonçalo R. Abecasis, Linda S. Adair, Carlos A. Aguilar‐Salinas, Marta E. Alarcón‐Riquelme, Ping An, Larissa Avilés‐Santa, Diane M. Becker, Lawrence J. Beilin, Sven Bergmann, Hans Bisgaard, Corri Black, Michael Boehnke, Eric Boerwinkle, Bernhard Böhm, Klaus Bønnelykke, Dorret I. Boomsma, Erwin P. Böttinger, Thomas A. Buchanan, Mickaël Canouil, Mark J. Caulfield, John C. Chambers, Daniel I. Chasman, Yii‐Der Ida Chen, Ching‐Yu Cheng, Francis S. Collins, Adolfo Correa, Francesco Cucca, H. Janaka de Silva, George Dedoussis, Sölve Elmståhl, Michele K. Evans, Ele Ferranni, Luigi Ferruci, José C. Florez, Paul W. Franks, Timothy M. Frayling, Philippe Froguel, Bruna Gigante, Mark O. Goodarzi, Penny Gordon‐Larsen, Harald Grallert, Niels Grarup, Sameline Grimsgaard, Leif Groop, Vilmundur Guðnason, Xiuqing Guo, Anders Hamsten, Torben Hansen, Caroline Hayward, Susan R. Heckbert, Bernardo Lessa Horta, Wei Huang, Erik Ingelsson, James S. Pankow, Jost B. Jonas, J. Wouter Jukema, Pontiano Kaleebu, Robert C. Kaplan, Sharon L. R. Kardia, Norihiro Kato, Sirkka Keinänen‐Kiukaanniemi, Bong-Jo Kim, Mika Kivimäki, Heikki A. Koistinen, Jaspal S. Kooner, Antje Körner, Péter Kovács, Diana Kuh, Meena Kumari, Zoltán Kutalik, Markku Laakso, Timo A. Lakka, Lenore J. Launer, Karin Leander, Huaixing Li, Lin Xu, Lars Lind, Cecilia M. Lindgren, Simin Liu, Ruth J. F. Loos, Patrik K. E. Magnusson, Anubha Mahajan, Andres Metspalu, Dennis O. Mook‐Kanamori, Trevor A. Mori, Patricia B. Munroe, Inger Njølstad, Jeffrey R. O’Connell, Albertine J. Oldehinkel, Ken K. Ong, Sandosh Padmanabhan, Oluf Pedersen, Craig E. Pennell, David J. Porteous, Peter P. Pramstaller, Michael A. Province, Bruce M. Psaty, Lu Qi, Leslie J. Raffel, Rainer Rauramaa, Susan Redline, Paul M. Ridker, Frits R. Rosendaal, Timo Saaristo, Manjinder S. Sandhu, Jouko Saramies, Neil Schneiderman, Peter E. H. Schwarz, Laura J. Scott, Elizabeth Selvin, Peter Sever, Xiao‐Ou Shu, P. Eline Slagboom, Kerrin S. Small, Blair H. Smith, Harold Snieder, Tamar Sofer, Thorkild I. A. Sørensen, Tim D. Spector, Alice Stanton, Claire J. Steves, Michael Stümvoll, Liang Sun, Yasuharu Tabara, E Shyong Tai, Nicholas J. Timpson, Anke Tönjes, Jaakko Tuomilehto, Teresa Tusié, Matti Uusitupa, Pim van der Harst, Cornelia M. van Duijn, Véronique Vitart, Péter Vollenweider, Tanja G. M. Vrijkotte, Lynne E. Wagenknecht, Mark Walker, Ya X. Wang, Richard M. Watanabe, Hugh Watkins, Wen Bin Wei, Ananda R. Wickremasinghe, Gonneke Willemsen, James F. Wilson, Tien Yin Wong, Jer‐Yuarn Wu, Anny H. Xiang, Lisa R. Yanek, Loïc Yengo, Mitsuhiro Yokota, Eleftheria Zeggini, Wei Zheng, Alan B. Zonderman, Jerome I. Rotter, Anna L. Gloyn, Mark I. McCarthy, Josée Dupuis, James B. Meigs, Robert A. Scott, Inga Prokopenko, Aaron Leong, Ching‐Ti Liu, Stephen C.J. Parker, Karen L. Mohlke, Claudia Langenberg, Eleanor Wheeler, Andrew P. Morris, Inês Barroso

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020

Typepreprint

Languageen

FieldBiochemistry, Genetics and Molecular Biology

TopicGenetic Associations and Epidemiology

Canadian institutionsCentre for Global Health Research

Fundersnot available

KeywordsGenetic architectureBiologyGenome-wide association studyQuantitative trait locusGenetic genealogyType 2 diabetesGeneticsGenetic associationTraitExpression quantitative trait lociAncestry-informative markerEvolutionary biologyGeneDiabetes mellitusGenotypeSingle-nucleotide polymorphismMedicinePopulationEndocrinology

DOI10.1101/2020.07.23.217646

Abstract

fetched live from OpenAlex

Abstract Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P <5×10 -8 ), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

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)0.005

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 score0.014

Distilled classifier scores by category (both heads)

Category	Codex	Gemma
Metaresearch	0.003	0.005
Meta-epidemiology (narrow)	0.000	0.000
Meta-epidemiology (broad)	0.001	0.001
Bibliometrics	0.001	0.002
Science and technology studies	0.001	0.001
Scholarly communication	0.002	0.001
Open science	0.000	0.001
Research integrity	0.001	0.001
Insufficient payload (model declined to judge)	0.003	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 head0.014

GPT teacher head0.227

Teacher spread0.213 · 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".

Quick stats

Citations10

Published2020

Admission routes1

Has abstractyes

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