Identifying the lungs as a susceptible site for allele-specific regulatory changes associated with type 1 diabetes risk.
Commun Biol
; 4(1): 1072, 2021 09 14.
Article
em En
| MEDLINE
| ID: mdl-34521982
ABSTRACT
Type 1 diabetes (T1D) etiology is complex. We developed a machine learning approach that ranked the tissue-specific transcription regulatory effects for T1D SNPs and estimated their relative contributions to conversion to T1D by integrating case and control genotypes (Wellcome Trust Case Control Consortium and UK Biobank) with tissue-specific expression quantitative trait loci (eQTL) data. Here we show an eQTL (rs6679677) associated with changes to AP4B1-AS1 transcript levels in lung tissue makes the largest gene regulatory contribution to the risk of T1D development. Luciferase reporter assays confirmed allele-specific enhancer activity for the rs6679677 tagged locus in lung epithelial cells (i.e. A549 cells; C > A reduces expression, p = 0.005). Our results identify tissue-specific eQTLs for SNPs associated with T1D. The strongest tissue-specific eQTL effects were in the lung and may help explain associations between respiratory infections and risk of islet autoantibody seroconversion in young children.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
/
Diabetes Mellitus Tipo 1
/
Pulmão
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Humans
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Nova Zelândia