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A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
Natalie R. van Zuydam, Emma Ahlqvist, Niina Sandholm, Harshal Deshmukh, Nigel W. Rayner, Moustafa Abdalla, Claes Ladenvall, Daniel Ziemek, Eric B. Fauman, Neil R. Robertson, Paul McKeigue, Erkka Valo, Carol Forsblom, Valma Harjutsalo, Annalisa Perna, Erica Rurali, M. Loredana Marcovecchio, Robert P. Igo, Rany M. Salem, Norberto Perico, Maria Lajer, Annemari Käräjämäki, Minako Imamura, Michiaki Kubo, Atsushi Takahashi, Xueling Sim, Jianjun Liu, Rob M. van Dam, Guozhi Jiang, Claudia H.T. Tam, Andrea O. Y. Luk, Heung Man Lee, Cadmon K.P. Lim, Cheuk‐Chun Szeto, Wing Yee So, Juliana C.N. Chan, Su Fen Ang, Rajkumar Dorajoo, Ling Wang, Tan Si Hua Clara, Amy Jayne McKnight, Seamus Duffy, Marcus G. Pezzolesi, Michel Marre, Beata Gyorgy, Samy Hadjadj, Linda T. Hiraki, Tarunveer S. Ahluwalia, Peter Almgren, Christina‐Alexandra Schulz, Marju Orho‐Melander, Allan Linneberg, Cramer Christensen, Daniel R. Witte, Niels Grarup, Ivan Brandslund, Olle Melander, Andrew D. Paterson, David‐Alexandre Trégouët, Alexander P. Maxwell, Su Chi Lim, Ronald C.W., E Shyong Tai, Shiro Maeda, Valeriya Lyssenko, Andrzej S. Królewski, Stephen S. Rich, Joel N. Hirschhorn, José C. Florez, David B. Dunger, Oluf Pedersen, Torben Hansen, Peter Rossing, Giuseppe Remuzzi, M. Julia Brosnan, Per‐Henrik Groop, Helen M. Colhoun, Leif Groop, Mark I. McCarthy, Satu Koivula, T. Uggeldahl, Terje Forslund, A. Halonen, A. Koistinen, P. Koskiaho, M. Laukkanen, Juha Saltevo, Miia Tiihonen, M. Forsen, Helena Granlund, A.-C. Jönsson, B. Nyroos, Pentti Kinnunen, A. Orvola, Tapani Salonen, A. Vähänen, Kotka R. Paldanius, M Riihelä, L. Ryysy, Kemi H. Laukkanen, P. Nyländen, Anni Sademies, S. Anderson, Barbro Asplund, U. Byskata, P. Liedes, M. Kuusela, T. Virkkala, Anssi Nikkola, E. Ritola, Tapiola M. Niska, Harri Juhani Saarinen, Samaria E. Oukko-Ruponen, Tuula Virtanen, Viherlaakso A. Lyytinen, T. Simonen, Suutarila A. Kaprio, Jorma Kärkkäinen, B. Rantaeskola, Toolo P. Kääriäinen, J R Haaga, A.-L. Pietiläinen, Sanna Klemetti, T. Nyandoto, E. Rontu, Susanna Satuli-Autere, Korso R. Toivonen, H. Virtanen Lansimaki, Riitta Ahonen, M. Ivaska-Suomela, Anneli Jauhiainen, Martinlaakso M. Laine, T. Pellonpää, R. Puranen, Myyrmaki A. Airas, Juha Laakso, K. Rautavaara, Rekola M. Erola, E. Jatkola, Tikkurila R. Lönnblad, Anna Malm, Jyrki Mäkelä, E. Rautamo, P. Hentunen, J. Lagerstam, Maija Feodoroff, Daniel Gordin, Outi Heikkilä, Kustaa Hietala, J. Fagerudd, Minna A. Korolainen, L. Kyllönen, Janne Kytö, S. Lindh, Milla Rosengård‐Bärlund, Amanda Sandelin, Lena M. Thorn, Jaana Tuomikangas, T. Vesisenaho, Johan Wadén, V. Sipilä, Forssa T. Kalliomäki, J. Koskelainen, R. Nikkanen, N. Savolainen, Hannu Sulonen, E. Valtonen, Leena Norvio, Anne Hämäläinen, E. Toivanen, Jamsa A. Parta, I. Pirttiniemi, S. Aranko, Satu Ervasti, Ari Kuusisto, T. Leppälä, Katriina Nikkilä, L. Pekkonen, K. Jokelainen, Kristiina Kananen, Matti Karjalainen, Pentti Kemppainen, A.-M. Mankinen, A. Reponen, M. Sankari, Pauli Suominen, Anu K. Lappalainen, Maarit Liimatainen, J. Santaholma, Ari Aimolahti, Elisa Huovinen, V. Ilkka, M. Y. Lehtimäki, E. Pälikkö-Kontinen, Antti Vanhanen, E. Koskinen, Timo Siitonen, Erja Huttunen, Risto Ikäheimo, Pauli Karhapää, Päivi Kekäläinen, M. Laakso, Timo A. Lakka, E Lampainen, Leena Moilanen, Sanna Tanskanen, Leo Niskanen, U. Tuovinen, Ilkka Vauhkonen, Erkki Voutilainen, Yü Huang, Si Lok, Brian Tomlinson, Stephen Kwok‐Wing Tsui, Weichuan Yu, Kevin Y.L. Yip, Ting‐Fung Chan, Xiaodan Fan, Nelson L.S. Tang, Fangying Xie, Alex C.W. Ng, Grace P.Y. Cheung, Ming Wai Yeung, Fei Xie, Sen Zhang, Yu Pu, Meng Weng, David A. Savage, James D. Walker, Stephen Thomas, Giancarlo Viberti, A.J.M. Boulton, S. M. Marshall, Andrew Demaine, B. A. Millward, Steve Baín, Ville‐Petteri Mäkinen, Aila J. Ahola, Emma H. Dahlström, Markku Lehto, Raija Lithovius, Nicolae Mircea Panduru, Maija Parkkonen, Markku Saraheimo, Jenny Söderlund, Aino Soro‐Paavonen, Anna Syreeni, Nina Tolonen, Gareth J. McKay, Tamara Isakova, Candace Guiducci, Andrew M. Taylor, Daniel B. Mirel, Winfred W. Williams, Eoin Brennan, Denise M. Sadlier, Finian Martin, Catherine Godson, Lynne Mayer, Rose Gubitosi‐Klug, P. A. Bourne, Mark H. Schutta, M. E. Lackaye, Naina Sinha Gregory, Davida Kruger, J. Kimberly Jones, Arti Bhan, E. Golden, Lloyd Paul Aiello, Mary Larkin, David Nathan, G. Ziegler, Susan Caulder, C. Pittman, Louis M. Luttrell, Maria F. Lopes‐Virella, Mary L. Johnson, K. Gunyou, Richard M. Bergenstal, B. Vittetoe, William I. Sivitz, Nancy Flaherty, John P. Bantle, Susan Hitt, David Goldstein, Dean P. Hainsworth, Lori Cimino, Trevor J. Orchard, Christine Wigley, Samuel Dagogo‐Jack, Suzanne Strowig, Philip Raskin, Annette Barnie, Bernard Zinman, Robyn Fahlstrom, Jerry P. Palmer, J. Harth, Marsha Driscoll, Charlotte McDonald, Janie Lipps Hagan, Michael May, L. Levandoski, Neil H. White, P. Gatcomb, William V. Tamborlane, Daphne T. Adelman, Susan Colson, Mark E. Molitch, Gayle M. Lorenzi, Sunder Mudaliar, S. Johnsonbaugh, Ryan Miller, Janene L. Canady, David S. Schade, M.L. Bernal, John I. Malone, Anthony Morrison, Catherine Martin, William H. Herman, Rodica Pop‐Busui, Catherine C. Cowie, Ellen Leschek, Patricia A. Cleary, John M. Lachin, B. Zinman, Barbara H. Braffett, Mike Steffes, Valerie Arends, Barbara Blodi, Ronald Danis, Daniel Lawrence, Hugh Wabers, Elsayed Z. Soliman, Zhu‐Ming Zhang, Charles J. Campbell, Susan Hensley, Lisa Keasler, Mark Michael, Markus Albertini, Carine Boustany, Alexander Ehlgen, Martin Gerl, Jochen Huber, Corinna Schölch, Heike Zimdahl‐Gelling, Elisabet Agardh, Tord Ajanki, Nibal Al Maghrabi, Jan Apelqvist, Eva Bengtsson, Lisa Berglund, Harry Björckbacka, Ulrika Blom-Nilsson, Mattias Borell, Agneta Burström, Corrado Cilio, Magnus Cinthio, Karl Dreja, Pontus Dunér, Daniel Engelbertsen, João Fadista, Marı́a Gómez, Isabel Gonçalves, Bo Hedblad, Anna Hultgårdh, Martin E. Johansson, Cecilia Kennbäck, Jasmina Kravić, Åke Lernmark, Eero Lindholm, Charlotte Ling, Holger Luthman, Malin Neptin, Jan Nilsson, Peter M. Nilsson, Tobias Nilsson, Gunilla Nordin, Emilia Ottoson-Laakso, Annie Persson, Margaretha Persson, Mats-Åke Persson, Jacqueline Postma, Elisabeth Pranter, Sara Rattik, Gunnar Sterner, Lilian Tindberg, Maria Wigren, Anna V. Zetterqvist, Mikael Åkerlund, Gerd Östling, Timo Kanninen, Anni Ahonen-Bishopp, Anita Eliasson, Timo Herrala, Päivi Tikka-Kleemola, Anders Hamsten, Christer Betsholtz, A. Björkholm, Fariba Foroogh, Guillem Genové, Karl Gertow, Bruna Gigante, Bing He, Karin Leander, Olga McLeod, Maria Nastase-Mannila, Jaako Patrakka, Angela Silveira, Rona J. Strawbridge, Karl Tryggvason, Max Vikström, John Öhrvik, Anne‐May Österholm, Barbara Thorand, Christian Gieger, Harald Grallert, Tonia Ludwig, Barbara Nitz, Andrea L.C. Schneider, Rui Wang‐Sattler, Astrid Zierer, Ariela Benigni, Roberta Donadelli, Mariadomenica Lesti, Marina Noris, Rossella Piras, Piero Ruggenenti, Ludo Chassin, Neil Dalton, John Deanfield, Jane Horsford, Clare Rice, James H.F. Rudd, Neil Walker, Karen Whitehead, Max Wong, F. Dennette Adams, Tahira Akbar, J. J. F. Belch, Fiona Dove, A Ellingford, Bassam Farran, Mike Ferguson, Gary L. Henderson, J. Graeme Houston, Faisel Khan, Graham Leese, Yiyuan Liu, Shona Livingstone, Helen C. Looker, Margaret McCann, Stuart J. McGurnaghan, Andrew D. Morris, D. J. Newton, Ewan R. Pearson, G Reekie, Natalie Smith, Angela C. Shore, Kuni Aizawa, Claire Ball, Nick G. Bellenger, Francesco Casanova, Timothy M. Frayling, Phil Gates, Kim M. Gooding, Andrew T. Hattersley, R Ling, David M. Mawson, Robin Shandas, W. David Strain, Clare E. Thorn, Ulf Smith, Ann Hammarstedt, Hans Häring, Georgio Sesti, Emma Fagerholm, Maikki Parkkonen, Iiro Toppila, Veikko Salomaa, Aki S. Havulinna, Kati Kristiansson, Pia Okamo, Tomi Peltola, Markus Perola, Arto Pietilä, Samuli Ripatti, Marketta Taimi, Seppo Ylä‐Herttuala, Mohan Babu, Marike H. Dijkstra, Erika Gurzeler, Jenni Huusko, Ivana Kholová, Markku Laakso, Mari Merentie, Marja Poikolainen, Mark McCarthy, Chris Groves, Thorhildur Juliusdottir, Fredrik Karpe, Vasiliki Lagou, Will Rayner, Neil Robertson, Claudio Cobelli, Barbara Di Camillo, Francesca Finotello, Francesco Sambo, Gianna Toffolo, Emanuele Trifoglio, Riccardo Bellazzi, Nicola Barbarini, Mauro Bucalo, Christiana Larizza, Paolo Magni, Alberto Malovini, Simone Marini, Francesca Mulas, Silvana Quaglini, Lucia Sacchi, Francesca Vitali, Ele Ferrannini, Beatrice Boldrini, M. Kozàkovà, Andrea Mari, C. Morizzo, L.G.S. Mota, Andrea Natali, Carlo Palombo, Elena Venturi, Mark S. Walker, Francesca Pagliaccia, Bianca Rocca, Pirjo Nuutila, Johanna Haukkala, Juhani Knuuti, Anne Roivainen, Antti Saraste, Paul McKeague, Marco Colombo, Birgit Steckel-Hamann, Krister Bokvist, Sudha Shankar, Mélissa Thomas, Li‐Ming Gan, Suvi E. Heinonen, Ann‐Cathrine Jönsson‐Rylander, Remi A. Momo, Volker Schnecke, Robert J. Unwin, Anna Walentinsson, Carl Whatling, Everson Nogoceke, Ivan Formentini, Thomas H. Schindler, Piero Tortoli, Luca Bassi, Enrico Boni, Alessandro Dallai, Francesco Guidi, Matteo Lenge, Riccardo Matera, Alessandro Ramalli, Stefano Ricci, Jacopo Viti, Bernd Jablonka, D Crowther, Johann Gassenhuber, Sibylle Hess, Thomas Hübschle, Hans‐Paul Juretschke, Hartmut Rütten, Thorsten Sadowski, Paulus Wohlfart, Julia Brosnan, Valérie Clerin, Craig Hyde, Anders Mälarstig, Nick Pullen, Mera Tilley, Theresa Tuthill, Ciara Vangjeli
Bibliographic record
VenueDiabetes · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsHospital for Sick Children
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Mental HealthNatural Sciences and Engineering Research Council of CanadaNational Institutes of HealthAssociation Diabète Risque VasculaireSkånes universitetssjukhusTurun Yliopistollinen KeskussairaalaNovo Nordisk FondenSamfundet FolkhälsanDirektör Albert Påhlssons StiftelseFinska LäkaresällskapetDiabetesfondenChinese University of Hong KongFood and Health BureauVetenskapsrådetMedical Research CouncilSigne ja Ane Gyllenbergin SäätiöKnut och Alice Wallenbergs StiftelseFolkhälsanin TutkimussäätiöUniversità degli Studi di PadovaNational Medical Research CouncilLunds UniversitetHong Kong GovernmentWilhelm och Else Stockmanns StiftelseMinistry of Education, Culture, Sports, Science and TechnologySteno Diabetes Center CopenhagenEuropean CommissionPublic Health AgencyNovo NordiskNational Institute for Health and Care ResearchNational Heart, Lung, and Blood InstituteNIHR Cambridge Biomedical Research CentreHelsingin ja Uudenmaan SairaanhoitopiiriWellcome Trust
KeywordsType 2 diabetesGenome-wide association studyMedicineGenetic associationDiseaseDiabetes mellitusInternal medicineBioinformaticsSingle-nucleotide polymorphismGeneticsBiologyEndocrinologyGenotypeGene
Abstract
Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10−8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
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 imitationNot 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)0.002
Version: codex-gemma-dda1882f352aValidation 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 score0.020
Threshold uncertainty score0.528
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 head0.007
GPT teacher head0.231
Teacher spread0.224 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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
Citations197
Published2018
Admission routes2
Has abstractyes