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Genetic discovery and risk characterization in type 2 diabetes across diverse populations.


ABSTRACT: 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.

SUBMITTER: Polfus LM 

PROVIDER: S-EPMC8486151 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Genetic discovery and risk characterization in type 2 diabetes across diverse populations.

Polfus Linda M LM   Darst Burcu F BF   Highland Heather H   Sheng Xin X   Ng Maggie C Y MCY   Below Jennifer E JE   Petty Lauren L   Bien Stephanie S   Sim Xueling X   Wang Wei W   Fontanillas Pierre P   Patel Yesha Y   Preuss Michael M   Schurmann Claudia C   Du Zhaohui Z   Lu Yingchang Y   Rhie Suhn K SK   Mercader Joseph M JM   Tusie-Luna Teresa T   González-Villalpando Clicerio C   Orozco Lorena L   Spracklen Cassandra N CN   Cade Brian E BE   Jensen Richard A RA   Sun Meng M   Joo Yoonjung Yoonie YY   An Ping P   Yanek Lisa R LR   Bielak Lawrence F LF   Tajuddin Salman S   Nicolas Aude A   Chen Guanjie G   Raffield Laura L   Guo Xiuqing X   Chen Wei-Min WM   Nadkarni Girish N GN   Graff Mariaelisa M   Tao Ran R   Pankow James S JS   Daviglus Martha M   Qi Qibin Q   Boerwinkle Eric A EA   Liu Simin S   Phillips Lawrence S LS   Peters Ulrike U   Carlson Chris C   Wikens Lynne R LR   Marchand Loic Le LL   North Kari E KE   Buyske Steven S   Kooperberg Charles C   Loos Ruth J F RJF   Stram Daniel O DO   Haiman Christopher A CA  

HGG advances 20210309 2


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 a  ...[more]

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