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Review
. 2022 Aug;10(8):597-608.
doi: 10.1016/S2213-8587(22)00159-0. Epub 2022 Jun 17.

Type 1 diabetes in diverse ancestries and the use of genetic risk scores

Maria J Redondo  1 , Christopher R Gignoux  2 , Dana Dabelea  3 , William A Hagopian  4 , Suna Onengut-Gumuscu  5 , Richard A Oram  6 , Stephen S Rich  5
Affiliations
Review

Type 1 diabetes in diverse ancestries and the use of genetic risk scores

Maria J Redondo et al. Lancet Diabetes Endocrinol. 2022 Aug.

Abstract

Over 75 genetic loci within and outside of the HLA region influence type 1 diabetes risk. Genetic risk scores (GRS), which facilitate the integration of complex genetic information, have been developed in type 1 diabetes and incorporated into models and algorithms for classification, prognosis, and prediction of disease and response to preventive and therapeutic interventions. However, the development and validation of GRS across different ancestries is still emerging, as is knowledge on type 1 diabetes genetics in populations of diverse genetic ancestries. In this Review, we provide a summary of the current evidence on the evolutionary genetic variation in type 1 diabetes and the racial and ethnic differences in type 1 diabetes epidemiology, clinical characteristics, and preclinical course. We also discuss the influence of genetics on type 1 diabetes with differences across ancestries and the development and validation of GRS in various populations.

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Conflict of interest statement

Declaration of interests RAO received a grant from UK Medical Research Council to partner with Randox for type 1 diabetes GRS biochip development. This work was supported by National Institute of Health grants (grant number R01 DK124395, MJR, RAO, DD, and WAH; R01 DK121843, MJR, RAO, SOG, and SSR; R01 HG010297, CRG and SSR; R01 HG011345, CRG; R01 HL151152, CRG and SSR; DP3 DK111906, SSR; R01 DK122586, SSR; and U01 HG011723, SSR). Funding sources had no role in the writing of this review or the decision to submit the paper for publication. All other authors declare no competing interests. The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.

Figures

Figure 1:
Figure 1:. Prevalence of five well known HLA-DR-DQ haplotype groups that confer susceptibility or resistance to type 1 diabetes in five different world regions
It should be noted that there is additional within-region heterogeneity; for example, the HLA-DRB1*03-DQA1*05-DQB1*02 (DR3-DQ2) haplotype is very rare.
Figure 2:
Figure 2:. Performance of the GRS-2 for type 1 diabetes in different races and ethnicities in youth with diabetes participating in the SEARCH study
Autoantibody positive or insulin sensitive diabetes is labelled as diabetes type 1 in the x axis, autoantibody negative or insulin resistant diabetes is labelled as diabetes type 2 in the x axis.
See this image and copyright information in PMC

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