What is it about?
To date, genome-wide association studies (GWAS) in T1D from Caucasian populations have identified more than 80 non-MHC T1D susceptibility loci. Although these results provide an overview of the genetic basis of T1D, genetic predisposition in diverse populations remains unclear taking into account the differences in risk allele frequency and linkage disequilibrium (LD) patterns, phenotypic prevalence, as well as effect size in different ethnic groups. Genetic studies in non-Caucasian populations are necessary to fully uncover the risk loci and bring medical advances underlying T1D in all populations. We performed a GWAS of T1D in Chinese Han population with all diagnosed age of autoantibody positive T1D individuals.
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Why is it important?
Even though with clinical heterogeneity, we observed a high genetic correlation between early-onset and late-onset T1D cases (rg=0.87), as well as different autoantibody subgroups (rg≥0.90). We identified four loci associated with T1D risk reaching genome-wide significance in Chinese population, including two novel loci rs4320356 in butyrophilin subfamily (OR=1.26, P=2.70×10-8) and rs3802604 in GATA3 (OR=1.24, P=2.06×10-8), and two previously reported loci rs1770 in MHC (OR=4.28, P=2.25×10-232) and rs705699 in RAB5B (OR=1.46, P=7.48×10-20). Fine mapping in the MHC region revealed five independent variants, including a novel locus HLA-C position 275 (omnibus P=9.78×10−12) specific to Chinese population. Based on the identified eight variants in Chinese population, we can achieve an area under the curve (AUC) of 0.86 (0.85-0.88). Building a genetic score (GRS) with these variants, we observed the higher GRSs are associated with an earlier onset age (P=9.08×10−11) and lower fasting C-peptide level at diagnosis (P=7.19×10−3).
Perspectives
These implicated that our results would be helpful in screening or risk stratification of T1D as well as precision medicine of T1D in Chinese population, which needs further investigations of genetic factors in Asians
Kuanfeng Xu
Read the Original
This page is a summary of: Identification of Novel T1D Risk Loci and Their Association With Age and Islet Function at Diagnosis in Autoantibody-Positive T1D Individuals: Based on a Two-Stage Genome-Wide Association Study, Diabetes Care, May 2019, American Diabetes Association,
DOI: 10.2337/dc18-2023.
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