Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Abstract Context Both type 1 diabetes (T1D) and type 2 diabetes (T2D) have significant genetic contributions to risk and understanding their overlap can offer clinical insight. Objective We examined whether a T1D polygenic score (PS) was associated with a diagnosis of T2D in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods We constructed a T1D PS using 79 known single nucleotide polymorphisms associated with T1D risk. We analyzed 13 792 T2D cases and 14 169 controls from CHARGE cohorts to determine the association between the T1D PS and T2D prevalence. We validated findings in an independent sample of 2256 T2D cases and 27 052 controls from the Mass General Brigham Biobank (MGB Biobank). As secondary analyses in 5228 T2D cases from CHARGE, we used multivariable regression models to assess the association of the T1D PS with clinical outcomes associated with T1D. Results The T1D PS was not associated with T2D both in CHARGE (P = .15) and in the MGB Biobank (P = .87). The partitioned human leukocyte antigens only PS was associated with T2D in CHARGE (OR 1.02 per 1 SD increase in PS, 95% CI 1.01-1.03, P = .006) but not in the MGB Biobank. The T1D PS was weakly associated with insulin use (OR 1.007, 95% CI 1.001-1.012, P = .03) in CHARGE T2D cases but not with other outcomes. Conclusion In large biobank samples, a common variant PS for T1D was not consistently associated with prevalent T2D. However, possible heterogeneity in T2D cannot be ruled out and future studies are needed do subphenotyping.

Original publication

DOI

10.1210/jendso/bvad123

Type

Journal article

Journal

Journal of the Endocrine Society

Publisher

The Endocrine Society

Publication Date

09/10/2023

Volume

7