A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes
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 compl...
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| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/140035 |
| _version_ | 1826116614272057344 |
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| author | van Zuydam, Natalie R. Ahlqvist, Emma Sandholm, Niina Deshmukh, Harshal Rayner, N. William Abdalla, Moustafa Ladenvall, Claes Ziemek, Daniel Fauman, Eric Robertson, Neil R. McKeigue, Paul M. Valo, Erkka Forsblom, Carol Harjutsalo, Valma Perna, Annalisa Rurali, Erica Marcovecchio, M Loredana Igo, Robert P. Salem, Rany M. Perico, Norberto Lajer, Maria Käräjämäki, Annemari Imamura, Minako Kubo, Michiaki Takahashi, Atsushi Sim, Xueling Liu, Jianjun van Dam, Rob M. Jiang, Guozhi Tam, Claudia H. T. Luk, Andrea O. Y. Lee, Heung Man Lim, Cadmon K. P. Szeto, Cheuk Chun So, Wing Yee Chan, Juliana C. N. Ang, Su Fen Dorajoo, Rajkumar Wang, Ling Clara, Tan Si Hua McKnight, Amy-Jayne Duffy, Seamus Pezzolesi, Marcus G. Marre, Michel Gyorgy, Beata Hadjadj, Samy Hiraki, Linda T. Ahluwalia, Tarunveer S. Almgren, Peter Schulz, Christina-Alexandra Orho-Melander, Marju Linneberg, Allan Christensen, Cramer Witte, Daniel R. Grarup, Niels Brandslund, Ivan Melander, Olle Paterson, Andrew D. Tregouet, David Maxwell, Alexander P. Lim, Su Chi Ma, Ronald C. W. Tai, E. Shyong Maeda, Shiro Lyssenko, Valeriya Tuomi, Tiinamaija Krolewski, Andrzej S. Rich, Stephen S. Hirschhorn, Joel N. Florez, Jose C. Dunger, David Pedersen, Oluf Hansen, Torben Rossing, Peter Remuzzi, Giuseppe Brosnan, Mary Julia Palmer, Colin N. A. Groop, Per-Henrik Colhoun, Helen M. Groop, Leif C. McCarthy, Mark I. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) van Zuydam, Natalie R. Ahlqvist, Emma Sandholm, Niina Deshmukh, Harshal Rayner, N. William Abdalla, Moustafa Ladenvall, Claes Ziemek, Daniel Fauman, Eric Robertson, Neil R. McKeigue, Paul M. Valo, Erkka Forsblom, Carol Harjutsalo, Valma Perna, Annalisa Rurali, Erica Marcovecchio, M Loredana Igo, Robert P. Salem, Rany M. Perico, Norberto Lajer, Maria Käräjämäki, Annemari Imamura, Minako Kubo, Michiaki Takahashi, Atsushi Sim, Xueling Liu, Jianjun van Dam, Rob M. Jiang, Guozhi Tam, Claudia H. T. Luk, Andrea O. Y. Lee, Heung Man Lim, Cadmon K. P. Szeto, Cheuk Chun So, Wing Yee Chan, Juliana C. N. Ang, Su Fen Dorajoo, Rajkumar Wang, Ling Clara, Tan Si Hua McKnight, Amy-Jayne Duffy, Seamus Pezzolesi, Marcus G. Marre, Michel Gyorgy, Beata Hadjadj, Samy Hiraki, Linda T. Ahluwalia, Tarunveer S. Almgren, Peter Schulz, Christina-Alexandra Orho-Melander, Marju Linneberg, Allan Christensen, Cramer Witte, Daniel R. Grarup, Niels Brandslund, Ivan Melander, Olle Paterson, Andrew D. Tregouet, David Maxwell, Alexander P. Lim, Su Chi Ma, Ronald C. W. Tai, E. Shyong Maeda, Shiro Lyssenko, Valeriya Tuomi, Tiinamaija Krolewski, Andrzej S. Rich, Stephen S. Hirschhorn, Joel N. Florez, Jose C. Dunger, David Pedersen, Oluf Hansen, Torben Rossing, Peter Remuzzi, Giuseppe Brosnan, Mary Julia Palmer, Colin N. A. Groop, Per-Henrik Colhoun, Helen M. Groop, Leif C. McCarthy, Mark I. |
| author_sort | van Zuydam, Natalie R. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T04:14:36Z |
| format | Journal Article |
| id | ntu-10356/140035 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:14:36Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1400352020-05-26T05:19:51Z A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes van Zuydam, Natalie R. Ahlqvist, Emma Sandholm, Niina Deshmukh, Harshal Rayner, N. William Abdalla, Moustafa Ladenvall, Claes Ziemek, Daniel Fauman, Eric Robertson, Neil R. McKeigue, Paul M. Valo, Erkka Forsblom, Carol Harjutsalo, Valma Perna, Annalisa Rurali, Erica Marcovecchio, M Loredana Igo, Robert P. Salem, Rany M. Perico, Norberto Lajer, Maria Käräjämäki, Annemari Imamura, Minako Kubo, Michiaki Takahashi, Atsushi Sim, Xueling Liu, Jianjun van Dam, Rob M. Jiang, Guozhi Tam, Claudia H. T. Luk, Andrea O. Y. Lee, Heung Man Lim, Cadmon K. P. Szeto, Cheuk Chun So, Wing Yee Chan, Juliana C. N. Ang, Su Fen Dorajoo, Rajkumar Wang, Ling Clara, Tan Si Hua McKnight, Amy-Jayne Duffy, Seamus Pezzolesi, Marcus G. Marre, Michel Gyorgy, Beata Hadjadj, Samy Hiraki, Linda T. Ahluwalia, Tarunveer S. Almgren, Peter Schulz, Christina-Alexandra Orho-Melander, Marju Linneberg, Allan Christensen, Cramer Witte, Daniel R. Grarup, Niels Brandslund, Ivan Melander, Olle Paterson, Andrew D. Tregouet, David Maxwell, Alexander P. Lim, Su Chi Ma, Ronald C. W. Tai, E. Shyong Maeda, Shiro Lyssenko, Valeriya Tuomi, Tiinamaija Krolewski, Andrzej S. Rich, Stephen S. Hirschhorn, Joel N. Florez, Jose C. Dunger, David Pedersen, Oluf Hansen, Torben Rossing, Peter Remuzzi, Giuseppe Brosnan, Mary Julia Palmer, Colin N. A. Groop, Per-Henrik Colhoun, Helen M. Groop, Leif C. McCarthy, Mark I. Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Diabetes Diabetic Kidney Disease 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. ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore) 2020-05-26T05:19:51Z 2020-05-26T05:19:51Z 2018 Journal Article van Zuydam, N. R., Ahlqvist, E., Sandholm, N., Deshmukh, H., Rayner, N. W., Abdalla, M., . . . McCarthy, M. I. (2018). A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes. Diabetes, 67(7), 1414-1427. doi:10.2337/db17-0914 0012-1797 https://hdl.handle.net/10356/140035 10.2337/db17-0914 29703844 7 67 1414 1427 en Diabetes © 2018 The American Diabetes Association. All rights reserved. |
| spellingShingle | Science::Medicine Diabetes Diabetic Kidney Disease van Zuydam, Natalie R. Ahlqvist, Emma Sandholm, Niina Deshmukh, Harshal Rayner, N. William Abdalla, Moustafa Ladenvall, Claes Ziemek, Daniel Fauman, Eric Robertson, Neil R. McKeigue, Paul M. Valo, Erkka Forsblom, Carol Harjutsalo, Valma Perna, Annalisa Rurali, Erica Marcovecchio, M Loredana Igo, Robert P. Salem, Rany M. Perico, Norberto Lajer, Maria Käräjämäki, Annemari Imamura, Minako Kubo, Michiaki Takahashi, Atsushi Sim, Xueling Liu, Jianjun van Dam, Rob M. Jiang, Guozhi Tam, Claudia H. T. Luk, Andrea O. Y. Lee, Heung Man Lim, Cadmon K. P. Szeto, Cheuk Chun So, Wing Yee Chan, Juliana C. N. Ang, Su Fen Dorajoo, Rajkumar Wang, Ling Clara, Tan Si Hua McKnight, Amy-Jayne Duffy, Seamus Pezzolesi, Marcus G. Marre, Michel Gyorgy, Beata Hadjadj, Samy Hiraki, Linda T. Ahluwalia, Tarunveer S. Almgren, Peter Schulz, Christina-Alexandra Orho-Melander, Marju Linneberg, Allan Christensen, Cramer Witte, Daniel R. Grarup, Niels Brandslund, Ivan Melander, Olle Paterson, Andrew D. Tregouet, David Maxwell, Alexander P. Lim, Su Chi Ma, Ronald C. W. Tai, E. Shyong Maeda, Shiro Lyssenko, Valeriya Tuomi, Tiinamaija Krolewski, Andrzej S. Rich, Stephen S. Hirschhorn, Joel N. Florez, Jose C. Dunger, David Pedersen, Oluf Hansen, Torben Rossing, Peter Remuzzi, Giuseppe Brosnan, Mary Julia Palmer, Colin N. A. Groop, Per-Henrik Colhoun, Helen M. Groop, Leif C. McCarthy, Mark I. A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes |
| title | A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes |
| title_full | A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes |
| title_fullStr | A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes |
| title_full_unstemmed | A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes |
| title_short | A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes |
| title_sort | genome wide association study of diabetic kidney disease in subjects with type 2 diabetes |
| topic | Science::Medicine Diabetes Diabetic Kidney Disease |
| url | https://hdl.handle.net/10356/140035 |
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genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT pedersenoluf genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT hansentorben genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT rossingpeter genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT remuzzigiuseppe genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT brosnanmaryjulia genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT palmercolinna genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT groopperhenrik genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT colhounhelenm genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT groopleifc genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes AT mccarthymarki genomewideassociationstudyofdiabetickidneydiseaseinsubjectswithtype2diabetes |