Effects of parental autoimmune diseases on type 1 diabetes in offspring can be partially explained by HLA and non-HLA polymorphisms

Wang, Feiyi, Liu, Aoxing, Yang, Zhiyu, Vartiainen, Pekka, Jukarainen, Sakari, Koskela, Satu, Oram, Richard, Allen, Lowri, Ritari, Jarmo, Partanen, Jukka, FinnGen, Perola, Markus, Tuomi, Tiinamaija and Ganna, Andrea 2025. Effects of parental autoimmune diseases on type 1 diabetes in offspring can be partially explained by HLA and non-HLA polymorphisms. Cell Genomics , 100854. 10.1016/j.xgen.2025.100854

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Abstract

Type 1 diabetes (T1D) and other autoimmune diseases (AIDs) often co-occur in families. Leveraging data from 58,284 family trios in Finnish nationwide registers (FinRegistry), we identified that, of 50 parental AIDs examined, 15 were associated with an increased T1D risk in offspring. These identified epidemiological associations were further assessed in 470,000 genotyped Finns from the FinnGen study through comprehensive genetic analyses, partitioned into human leukocyte antigen (HLA) and non-HLA variations. Using FinnGen's 12,563 trios, a within-family polygenic transmission analysis demonstrated that the aggregation of many parental AIDs with offspring T1D can be partially explained by HLA and non-HLA polymorphisms in a disease-dependent manner. We therefore proposed a parental polygenic score (PGS), incorporating both HLA and non-HLA polymorphisms, to characterize the cumulative risk pattern of T1D in offspring. This raises an intriguing possibility of using parental PGS, in conjunction with clinical diagnoses, to inform individuals about T1D risk in their offspring. [Abstract copyright: Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.]

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Cell Press
ISSN:	2666-979X
Date of First Compliant Deposit:	2 June 2025
Date of Acceptance:	31 March 2025
Last Modified:	02 Jun 2025 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/178638

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