Rare Genetic Variants of Large Effect Influence Risk of Type 1 Diabetes.

ABSTRACT: Most replicated genetic determinants for type 1 diabetes are common (minor allele frequency [MAF] >5%). We aimed to identify novel rare or low-frequency (MAF <5%) single nucleotide polymorphisms with large effects on risk of type 1 diabetes. We undertook deep imputation of genotyped data followed by genome-wide association testing and meta-analysis of 9,358 type 1 diabetes case and 15,705 control subjects from 12 European cohorts. Candidate variants were replicated in a separate cohort of 4,329 case and 9,543 control subjects. Our meta-analysis identified 27 independent variants outside the MHC, among which 3 were novel and had MAF <5%. Three of these variants replicated with P _replication < 0.05 and P _combined < P _discovery In silico a

SUBMITTER: Forgetta V 

PROVIDER: S-EPMC7085253 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature