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

The 23andMe Research Team, DIAMANTE Hispanic/Latino Consortium, MEta-analysis of type 2 DIabetes in African Americans Consortium

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number100029
JournalHuman Genetics and Genomics Advances
Volume2
Issue number2
DOIs
StatePublished - Apr 8 2021

Bibliographical note

Funding Information:
This research was supported by National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) grant R56HG010297 and was conducted using the UK Biobank Resource under application number 42195. Study-specific acknowledgments can be found in the Supplemental acknowledgments .

Funding Information:
This research was supported by National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) grant R56HG010297 and was conducted using the UK Biobank Resource under application number 42195. Study-specific acknowledgments can be found in the Supplemental acknowledgments. W.W. and P.F. are employees of 23andMe Inc. and have stock, stock options, or both in 23andMe. For L.S.P.: Diasyst, Inc. co-founder (equity and stock) Board of Directors or officer Diasyst, Inc. President, secretary, chief medical and scientific officer royalties from Emory. President, secretary, chief medical and scientific officer industry funds to Emory and/or the Atlanta Research and Education Foundation, Inc. (related to the Atlanta VA Medical Center) for research support. Eli Lilly, Novartis, Merck, Amylin, Novo Nordisk, Diasome, Roche, AbbVie, Sanofi-Aventis, Vascular Pharma, Janssen, GlaxoSmithKline, Pfizer, Kowa Investigator - diabetes studies (research support only), Boehringer-Ingelheim, Merck, Novartis, Takeda, Janssen, Profil Research Institute Speaker, and/or Scientific Advisory Board, and/or Consultant. All other authors declare no competing interests.

Publisher Copyright:
© 2021 The Author(s)

Keywords

  • Genetic Risk Score
  • Type 2 Diabetes

PubMed: MeSH publication types

  • Journal Article

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