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Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis
We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program, DIAMANTE, Biobank Japan, and other studies. We report 568 associations, including 286 autosomal, 7 X chromosomal, and 25 identified in a...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343592/ https://www.ncbi.nlm.nih.gov/pubmed/32541925 http://dx.doi.org/10.1038/s41588-020-0637-y |
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| author | Vujkovic, Marijana Keaton, Jacob M. Lynch, Julie A. Miller, Donald R. Zhou, Jin Tcheandjieu, Catherine Huffman, Jennifer E. Assimes, Themistocles L. Lorenz, Kim Zhu, Xiang Hilliard, Austin T. Judy, Renae L. Huang, Jie Lee, Kyung M. Klarin, Derek Pyarajan, Saiju Danesh, John Melander, Olle Rasheed, Asif Mallick, Nadeem H. Hameed, Shahid Qureshi, Irshad H. Afzal, Muhammad Naeem Malik, Uzma Jalal, Anjum Abbas, Shahid Sheng, Xin Gao, Long Kaestner, Klaus H. Susztak, Katalin Sun, Yan V. DuVall, Scott L. Cho, Kelly Lee, Jennifer S. Gaziano, J. Michael Phillips, Lawrence S. Meigs, James B. Reaven, Peter D. Wilson, Peter W. Edwards, Todd L. Rader, Daniel J. Damrauer, Scott M. O’Donnell, Christopher J. Tsao, Philip S. Chang, Kyong-Mi Voight, Benjamin F. Saleheen, Danish |
| author_facet | Vujkovic, Marijana Keaton, Jacob M. Lynch, Julie A. Miller, Donald R. Zhou, Jin Tcheandjieu, Catherine Huffman, Jennifer E. Assimes, Themistocles L. Lorenz, Kim Zhu, Xiang Hilliard, Austin T. Judy, Renae L. Huang, Jie Lee, Kyung M. Klarin, Derek Pyarajan, Saiju Danesh, John Melander, Olle Rasheed, Asif Mallick, Nadeem H. Hameed, Shahid Qureshi, Irshad H. Afzal, Muhammad Naeem Malik, Uzma Jalal, Anjum Abbas, Shahid Sheng, Xin Gao, Long Kaestner, Klaus H. Susztak, Katalin Sun, Yan V. DuVall, Scott L. Cho, Kelly Lee, Jennifer S. Gaziano, J. Michael Phillips, Lawrence S. Meigs, James B. Reaven, Peter D. Wilson, Peter W. Edwards, Todd L. Rader, Daniel J. Damrauer, Scott M. O’Donnell, Christopher J. Tsao, Philip S. Chang, Kyong-Mi Voight, Benjamin F. Saleheen, Danish |
| author_sort | Vujkovic, Marijana |
| collection | PubMed |
| description | We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program, DIAMANTE, Biobank Japan, and other studies. We report 568 associations, including 286 autosomal, 7 X chromosomal, and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D-associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD), and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease, CKD, PAD, and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes. |
| format | Online Article Text |
| id | pubmed-7343592 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-73435922020-12-15 Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis Vujkovic, Marijana Keaton, Jacob M. Lynch, Julie A. Miller, Donald R. Zhou, Jin Tcheandjieu, Catherine Huffman, Jennifer E. Assimes, Themistocles L. Lorenz, Kim Zhu, Xiang Hilliard, Austin T. Judy, Renae L. Huang, Jie Lee, Kyung M. Klarin, Derek Pyarajan, Saiju Danesh, John Melander, Olle Rasheed, Asif Mallick, Nadeem H. Hameed, Shahid Qureshi, Irshad H. Afzal, Muhammad Naeem Malik, Uzma Jalal, Anjum Abbas, Shahid Sheng, Xin Gao, Long Kaestner, Klaus H. Susztak, Katalin Sun, Yan V. DuVall, Scott L. Cho, Kelly Lee, Jennifer S. Gaziano, J. Michael Phillips, Lawrence S. Meigs, James B. Reaven, Peter D. Wilson, Peter W. Edwards, Todd L. Rader, Daniel J. Damrauer, Scott M. O’Donnell, Christopher J. Tsao, Philip S. Chang, Kyong-Mi Voight, Benjamin F. Saleheen, Danish Nat Genet Article We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program, DIAMANTE, Biobank Japan, and other studies. We report 568 associations, including 286 autosomal, 7 X chromosomal, and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D-associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD), and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease, CKD, PAD, and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes. 2020-06-15 2020-07 /pmc/articles/PMC7343592/ /pubmed/32541925 http://dx.doi.org/10.1038/s41588-020-0637-y Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Vujkovic, Marijana Keaton, Jacob M. Lynch, Julie A. Miller, Donald R. Zhou, Jin Tcheandjieu, Catherine Huffman, Jennifer E. Assimes, Themistocles L. Lorenz, Kim Zhu, Xiang Hilliard, Austin T. Judy, Renae L. Huang, Jie Lee, Kyung M. Klarin, Derek Pyarajan, Saiju Danesh, John Melander, Olle Rasheed, Asif Mallick, Nadeem H. Hameed, Shahid Qureshi, Irshad H. Afzal, Muhammad Naeem Malik, Uzma Jalal, Anjum Abbas, Shahid Sheng, Xin Gao, Long Kaestner, Klaus H. Susztak, Katalin Sun, Yan V. DuVall, Scott L. Cho, Kelly Lee, Jennifer S. Gaziano, J. Michael Phillips, Lawrence S. Meigs, James B. Reaven, Peter D. Wilson, Peter W. Edwards, Todd L. Rader, Daniel J. Damrauer, Scott M. O’Donnell, Christopher J. Tsao, Philip S. Chang, Kyong-Mi Voight, Benjamin F. Saleheen, Danish Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis |
| title | Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis |
| title_full | Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis |
| title_fullStr | Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis |
| title_full_unstemmed | Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis |
| title_short | Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis |
| title_sort | discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343592/ https://www.ncbi.nlm.nih.gov/pubmed/32541925 http://dx.doi.org/10.1038/s41588-020-0637-y |
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