[논문]Functional annotation of noncoding causal variants in autoimmune diseases

Yousefian-Jazi, Ali; Jung, Jieun; Choi, Jung Kyoon; Choi, Jinwook

doi:10.1016/j.ygeno.2019.07.006

[해외논문] Functional annotation of noncoding causal variants in autoimmune diseases 원문보기

Genomics, v.112 no.2, 2020년, pp.1208 - 1213

Yousefian-Jazi, Ali (Interdisciplinary Program, Bioengineering Major, Graduate School, Seoul National University) , Jung, Jieun (Interdisciplinary Program, Bioengineering Major, Graduate School, Seoul National University) , Choi, Jung Kyoon (Department of Bio and Brain Engineering, KAIST) , Choi, Jinwook (Department of Biomedical Engineering, College of Medicine, Seoul National University)

Abstract ▼ AI-Helper

Abstract Interpretation of noncoding disease variants, which comprise the vast majority of Genome-wide association studies (GWAS) hits, remains a momentous challenge due to haplotype structure and our limited understanding of the mechanisms and physiological contexts of noncoding elements. GWAS have identified loci underlying human diseases, but assigning the causal nucleotide changes still remain a controversial issue. Here we addressed these issues through the combination of high-density genotyping and epigenomic data using a random forest model to discover the noncoding causal variants. Focusing on autoimmune diseases, we triaged putative causal variants for atopic dermatitis and inflammatory bowel diseases. Making a filtering pipeline, we found three interesting single nucleotide polymorphisms (rs1800630, rs1799964 and rs4796793) in the upstream site of TNF and STAT3 genes, two frequent genes shared in some autoimmune diseases, and show how those variants affect on TNF and STAT3 expression levels. All data and source codes related to this manuscript are available at https://github.com/jieunjung511/Autoimmune-research. Highlights We looked for shared noncoding causal genetic loci for autoimmune diseases A random forest model was trained on genetic and epigenetic features of pathogenic variants. Our model encompassed both promoter and enhancer sites by considering the associations between them. We identified three SNPs (rs1800630, rs1799964 and rs4796793) in the upstream regions of TNF and STAT3 genes as the putative causal variants for atopic dermatitis and inflammatory bowel diseases.

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