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Genetic discovery and risk characterization in type 2 diabetes across diverse populations
Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawai...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486151/ https://www.ncbi.nlm.nih.gov/pubmed/34604815 http://dx.doi.org/10.1016/j.xhgg.2021.100029 |
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author | Polfus, Linda M. Darst, Burcu F. Highland, Heather Sheng, Xin Ng, Maggie C.Y. Below, Jennifer E. Petty, Lauren Bien, Stephanie Sim, Xueling Wang, Wei Fontanillas, Pierre Patel, Yesha Preuss, Michael Schurmann, Claudia Du, Zhaohui Lu, Yingchang Rhie, Suhn K. Mercader, Joseph M. Tusie-Luna, Teresa González-Villalpando, Clicerio Orozco, Lorena Spracklen, Cassandra N. Cade, Brian E. Jensen, Richard A. Sun, Meng Joo, Yoonjung Yoonie An, Ping Yanek, Lisa R. Bielak, Lawrence F. Tajuddin, Salman Nicolas, Aude Chen, Guanjie Raffield, Laura Guo, Xiuqing Chen, Wei-Min Nadkarni, Girish N. Graff, Mariaelisa Tao, Ran Pankow, James S. Daviglus, Martha Qi, Qibin Boerwinkle, Eric A. Liu, Simin Phillips, Lawrence S. Peters, Ulrike Carlson, Chris Wikens, Lynne R. Le Marchand, Loic North, Kari E. Buyske, Steven Kooperberg, Charles Loos, Ruth J.F. Stram, Daniel O. Haiman, Christopher A. |
author_facet | Polfus, Linda M. Darst, Burcu F. Highland, Heather Sheng, Xin Ng, Maggie C.Y. Below, Jennifer E. Petty, Lauren Bien, Stephanie Sim, Xueling Wang, Wei Fontanillas, Pierre Patel, Yesha Preuss, Michael Schurmann, Claudia Du, Zhaohui Lu, Yingchang Rhie, Suhn K. Mercader, Joseph M. Tusie-Luna, Teresa González-Villalpando, Clicerio Orozco, Lorena Spracklen, Cassandra N. Cade, Brian E. Jensen, Richard A. Sun, Meng Joo, Yoonjung Yoonie An, Ping Yanek, Lisa R. Bielak, Lawrence F. Tajuddin, Salman Nicolas, Aude Chen, Guanjie Raffield, Laura Guo, Xiuqing Chen, Wei-Min Nadkarni, Girish N. Graff, Mariaelisa Tao, Ran Pankow, James S. Daviglus, Martha Qi, Qibin Boerwinkle, Eric A. Liu, Simin Phillips, Lawrence S. Peters, Ulrike Carlson, Chris Wikens, Lynne R. Le Marchand, Loic North, Kari E. Buyske, Steven Kooperberg, Charles Loos, Ruth J.F. Stram, Daniel O. Haiman, Christopher A. |
author_sort | Polfus, Linda M. |
collection | PubMed |
description | Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the TGFB1 gene (rs11466334, risk allele frequency (RAF) = 6.8%, odds ratio [OR] = 1.27, p = 2.06 × 10(−8)), which replicated in independent studies of African ancestry (p = 6.26 × 10(−23)). We identified a multiethnic risk variant in the BACE2 gene (rs13052926, RAF = 14.1%, OR = 1.08, p = 5.75 × 10(−9)), which also replicated in independent studies (p = 3.45 × 10(−4)). We also observed a significant difference in the performance of a multiethnic genetic risk score (GRS) across population groups (p(heterogeneity) = 3.85 × 10(−20)). Comparing individuals in the top GRS risk category (40%–60%), the OR was highest in Asians (OR = 3.08) and European (OR = 2.94) ancestry populations, followed by Hispanic (OR = 2.39), Native Hawaiian (OR = 2.02), and African ancestry (OR = 1.57) populations. These findings underscore the importance of genetic discovery and risk characterization in diverse populations and the urgent need to further increase representation of non-European ancestry individuals in genetics research to improve genetic-based risk prediction across populations. |
format | Online Article Text |
id | pubmed-8486151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84861512021-10-01 Genetic discovery and risk characterization in type 2 diabetes across diverse populations Polfus, Linda M. Darst, Burcu F. Highland, Heather Sheng, Xin Ng, Maggie C.Y. Below, Jennifer E. Petty, Lauren Bien, Stephanie Sim, Xueling Wang, Wei Fontanillas, Pierre Patel, Yesha Preuss, Michael Schurmann, Claudia Du, Zhaohui Lu, Yingchang Rhie, Suhn K. Mercader, Joseph M. Tusie-Luna, Teresa González-Villalpando, Clicerio Orozco, Lorena Spracklen, Cassandra N. Cade, Brian E. Jensen, Richard A. Sun, Meng Joo, Yoonjung Yoonie An, Ping Yanek, Lisa R. Bielak, Lawrence F. Tajuddin, Salman Nicolas, Aude Chen, Guanjie Raffield, Laura Guo, Xiuqing Chen, Wei-Min Nadkarni, Girish N. Graff, Mariaelisa Tao, Ran Pankow, James S. Daviglus, Martha Qi, Qibin Boerwinkle, Eric A. Liu, Simin Phillips, Lawrence S. Peters, Ulrike Carlson, Chris Wikens, Lynne R. Le Marchand, Loic North, Kari E. Buyske, Steven Kooperberg, Charles Loos, Ruth J.F. Stram, Daniel O. Haiman, Christopher A. HGG Adv Article Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the TGFB1 gene (rs11466334, risk allele frequency (RAF) = 6.8%, odds ratio [OR] = 1.27, p = 2.06 × 10(−8)), which replicated in independent studies of African ancestry (p = 6.26 × 10(−23)). We identified a multiethnic risk variant in the BACE2 gene (rs13052926, RAF = 14.1%, OR = 1.08, p = 5.75 × 10(−9)), which also replicated in independent studies (p = 3.45 × 10(−4)). We also observed a significant difference in the performance of a multiethnic genetic risk score (GRS) across population groups (p(heterogeneity) = 3.85 × 10(−20)). Comparing individuals in the top GRS risk category (40%–60%), the OR was highest in Asians (OR = 3.08) and European (OR = 2.94) ancestry populations, followed by Hispanic (OR = 2.39), Native Hawaiian (OR = 2.02), and African ancestry (OR = 1.57) populations. These findings underscore the importance of genetic discovery and risk characterization in diverse populations and the urgent need to further increase representation of non-European ancestry individuals in genetics research to improve genetic-based risk prediction across populations. Elsevier 2021-03-09 /pmc/articles/PMC8486151/ /pubmed/34604815 http://dx.doi.org/10.1016/j.xhgg.2021.100029 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Polfus, Linda M. Darst, Burcu F. Highland, Heather Sheng, Xin Ng, Maggie C.Y. Below, Jennifer E. Petty, Lauren Bien, Stephanie Sim, Xueling Wang, Wei Fontanillas, Pierre Patel, Yesha Preuss, Michael Schurmann, Claudia Du, Zhaohui Lu, Yingchang Rhie, Suhn K. Mercader, Joseph M. Tusie-Luna, Teresa González-Villalpando, Clicerio Orozco, Lorena Spracklen, Cassandra N. Cade, Brian E. Jensen, Richard A. Sun, Meng Joo, Yoonjung Yoonie An, Ping Yanek, Lisa R. Bielak, Lawrence F. Tajuddin, Salman Nicolas, Aude Chen, Guanjie Raffield, Laura Guo, Xiuqing Chen, Wei-Min Nadkarni, Girish N. Graff, Mariaelisa Tao, Ran Pankow, James S. Daviglus, Martha Qi, Qibin Boerwinkle, Eric A. Liu, Simin Phillips, Lawrence S. Peters, Ulrike Carlson, Chris Wikens, Lynne R. Le Marchand, Loic North, Kari E. Buyske, Steven Kooperberg, Charles Loos, Ruth J.F. Stram, Daniel O. Haiman, Christopher A. Genetic discovery and risk characterization in type 2 diabetes across diverse populations |
title | Genetic discovery and risk characterization in type 2 diabetes across diverse populations |
title_full | Genetic discovery and risk characterization in type 2 diabetes across diverse populations |
title_fullStr | Genetic discovery and risk characterization in type 2 diabetes across diverse populations |
title_full_unstemmed | Genetic discovery and risk characterization in type 2 diabetes across diverse populations |
title_short | Genetic discovery and risk characterization in type 2 diabetes across diverse populations |
title_sort | genetic discovery and risk characterization in type 2 diabetes across diverse populations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486151/ https://www.ncbi.nlm.nih.gov/pubmed/34604815 http://dx.doi.org/10.1016/j.xhgg.2021.100029 |
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