Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci.
Hui-Qi QuJingchun QuJonathan BradfieldLuc MarchandJoseph T GlessnerXiao ChangMichael E MarchJin LiJohn J ConnollyJeffrey D RoizenPatrick SleimanConstantin PolychronakosHakon H HakonarsonPublished in: Communications biology (2021)
Type 1 diabetes (T1D) patients with low genetic risk scores (GRS) may be non-autoimmune or autoimmune mediated by other genetic loci. The T1D-GRS2 provides us an opportunity to look into the genetic architecture of these patients. A total of 18,949 European individuals were included in this study, including 6599 T1D cases and 12,323 controls. 957 (14.5%) T1D patients were identified with low GRS (GRS < 8.43). The genome-wide association study on these patients identified 41 unreported loci. Two loci with common variants and 39 loci with rare variants were identified in this study. This study identified common SNPs associated with both low GRS T1D and expression levels of the interferon-α-induced MNDA gene, indicating the role of viral infection in T1D. Interestingly, 16 of the 41 unreported loci have been linked to autism spectrum disorder (ASD) by previous studies, suggesting that genes residing at these loci may underlie both T1D and autism.
Keyphrases
- genome wide
- genome wide association study
- autism spectrum disorder
- copy number
- type diabetes
- end stage renal disease
- dna methylation
- chronic kidney disease
- ejection fraction
- newly diagnosed
- genome wide association
- cardiovascular disease
- gene expression
- peritoneal dialysis
- prognostic factors
- oxidative stress
- patient reported
- drug induced
- diabetic rats
- insulin resistance
- working memory