TY - JOUR
T1 - Genetic discovery and risk characterization in type 2 diabetes across diverse populations
AU - The 23andMe Research Team
AU - DIAMANTE Hispanic/Latino Consortium
AU - MEta-analysis of type 2 DIabetes in African Americans Consortium
AU - Polfus, Linda M.
AU - Darst, Burcu F.
AU - Highland, Heather
AU - Sheng, Xin
AU - Ng, Maggie C.Y.
AU - Below, Jennifer E.
AU - Petty, Lauren
AU - Bien, Stephanie
AU - Sim, Xueling
AU - Wang, Wei
AU - Fontanillas, Pierre
AU - Patel, Yesha
AU - Preuss, Michael
AU - Schurmann, Claudia
AU - Du, Zhaohui
AU - Lu, Yingchang
AU - Rhie, Suhn K.
AU - Mercader, Joseph M.
AU - Tusie-Luna, Teresa
AU - González-Villalpando, Clicerio
AU - Orozco, Lorena
AU - Spracklen, Cassandra N.
AU - Cade, Brian E.
AU - Jensen, Richard A.
AU - Sun, Meng
AU - Joo, Yoonjung Yoonie
AU - An, Ping
AU - Yanek, Lisa R.
AU - Bielak, Lawrence F.
AU - Tajuddin, Salman
AU - Nicolas, Aude
AU - Chen, Guanjie
AU - Raffield, Laura
AU - Guo, Xiuqing
AU - Chen, Wei Min
AU - Nadkarni, Girish N.
AU - Graff, Mariaelisa
AU - Tao, Ran
AU - Pankow, James S.
AU - Daviglus, Martha
AU - Qi, Qibin
AU - Boerwinkle, Eric A.
AU - Liu, Simin
AU - Phillips, Lawrence S.
AU - Peters, Ulrike
AU - Carlson, Chris
AU - Wikens, Lynne R.
AU - Le Marchand, Loic
AU - North, Kari E.
AU - Buyske, Steven
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/4/8
Y1 - 2021/4/8
N2 - 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 (pheterogeneity = 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.
AB - 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 (pheterogeneity = 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.
KW - Genetic Risk Score
KW - Type 2 Diabetes
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U2 - 10.1016/j.xhgg.2021.100029
DO - 10.1016/j.xhgg.2021.100029
M3 - Article
C2 - 34604815
AN - SCOPUS:85111311121
SN - 2666-2477
VL - 2
JO - Human Genetics and Genomics Advances
JF - Human Genetics and Genomics Advances
IS - 2
M1 - 100029
ER -