在低多基因风险评分特征的 1 型糖尿病患者中 DLL1 的关联。

Association of DLL1 with type 1 diabetes in patients characterized by low polygenic risk score.

机构信息

The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Quantinuum Research LLC, San Diego, CA 92101, USA.

出版信息

Metabolism. 2021 Jan;114:154418. doi: 10.1016/j.metabol.2020.154418. Epub 2020 Nov 4.

DOI:10.1016/j.metabol.2020.154418

PMID:33157082

Abstract

Type 1 diabetes (T1D) is a heterogeneous disease. This study identified T1D cases with low polygenic risk score (PRS) to better represent T1D cases with less prominent autoimmune response (T1bD), and performed a gene-based association study to identify novel susceptibility loci in two independent cohorts, characterized by low PRS. The Notch ligand Delta-like 1 gene (DLL1) was identified with genome-wide significance in both cohorts, highlighting the roles of DLL1 genetic variants in T1D patients with low PRS, supported by functional evidence from a recent study by Rubey et al.

摘要

1 型糖尿病（T1D）是一种异质性疾病。本研究鉴定了低多基因风险评分（PRS）的 T1D 病例，以更好地代表自身免疫反应不明显的 T1D 病例（T1bD），并在两个具有低 PRS 的独立队列中进行了基于基因的关联研究，以鉴定新的易感基因座。Notch 配体 Delta-like 1 基因（DLL1）在两个队列中均达到全基因组显著性水平，突出了 DLL1 遗传变异在低 PRS 的 T1D 患者中的作用，这一结果得到了 Rubey 等人最近研究的功能证据的支持。