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Cited by 80Diabetes and associated disordersGenetic Associations and EpidemiologyDiabetes Management and Research

Utility of genetic risk scores in type 1 diabetes

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Luckett, Amber M., Weedon, Michael N., Hawkes, Gareth, Leslie, R. David, Oram, Richard A., Grant, Struan F. A.·2023·Diabetologia
DOI 10.1007/s00125-023-05955-yPMC PMC10390619
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Abstract

Iterative advances in understanding of the genetics of type 1 diabetes have identified >70 genetic regions associated with risk of the disease, including strong associations across the HLA class II region that account for >50% of heritability. The increased availability of genetic data combined with the decreased costs of generating these data, have facilitated the development of polygenic scores that aggregate risk variants from associated loci into a single number: either a genetic risk score (GRS) or a polygenic risk score (PRS). PRSs incorporate the risk of many possibly correlated variants from across the genome, even if they do not reach genome-wide significance, whereas GRSs estimate the cumulative contribution of a smaller subset of genetic variants that reach genome-wide significance. Type 1 diabetes GRSs have utility in diabetes classification, aiding discrimination between type 1 diabetes, type 2 diabetes and MODY. Type 1 diabetes GRSs are also being used in newborn screening studies to identify infants at risk of future presentation of the disease. Most early studies of type 1 diabetes genetics have been conducted in European ancestry populations, but, to develop accurate GRSs across diverse ancestries, large case–control cohorts from non-European populations are still needed. The current barriers to GRS implementation within healthcare are mainly related to a lack of guidance and knowledge on integration with other biomarkers and clinical variables. Once these limitations are addressed, there is huge potential for ‘test and treat’ approaches to be used to tailor care for individuals with type 1 diabetes. Graphical Abstract

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  • Many genetic risk studies have been performed in populations of European ancestry and discriminatory ability may differ in those of different ancestry.

    “As many genetic risk studies have been performed in populations of European ancestry and discriminatory ability may differ in those of different ancestry, more large case-control cohorts from non-European populations are still needed (82).”

    From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [82]

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Cited by

Sorted by citations

Authors
Luckett, A. M., Weedon, M. N., Hawkes, G., Leslie, R. D., Oram, R. A., & Grant, S. F. A.
Affiliations
  • University of Exeter (GB)
  • Queen Mary University of London (GB)
  • Children's Hospital of Philadelphia (US)
Corresponding author
  • Leslie, R. David
  • Oram, Richard A.
  • Grant, Struan F. A.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2023-07-13
Volume
66
Issue
9
Pages
1589-1600
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-023-05955-y
PMC
PMC10390619
OpenAlex
W4384126579
Cited by
80
References
10
Citations by year
2026: 19 · 2025: 43 · 2024: 17 · 2023: 1
FWCI
3.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
Funders
  • Children's Hospital of Philadelphia (Daniel B. Burke Chair for Diabetes Research)
  • Juvenile Diabetes Research Foundation United States of America (2-SRA-2002–1259-S-B, 2-SRA-2022–1258-M-B, 2-SRA-2022–1261-S-B, 3-SRA-2019–827-S-B, 3-SRA-2022–1241-S-B)
  • National Institute for Health and Care Research Exeter Biomedical Research Centre
  • Diabetes UK (Harry Keen Fellowship 16/0005529)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIH R01 DK121843–01, R01 DK122586, U01DK127382–01, UM1 DK126194)
  • The Larry M and Leona B Helmsley Charitable Trust
  • National Institute of Child Health and Human Development (R01 HD056465)
  • UK MRC (Confidence in concept award)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 1 diabetes, polygenic risk score, HLA class II, genetic risk variants, diabetes classification, newborn screening, ancestry diversity, test and treat, precision medicine
MeSH terms
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Infant, Newborn, Risk Factors, Biomarkers, Genetic Predisposition to Disease, Genome-Wide Association Study

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