Functional annotation of noncoding causal variants in autoimmune diseases

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

doi:10.1016/j.ygeno.2019.07.006

Functional annotation of noncoding causal variants in autoimmune diseases

Genomics. 2020 Mar;112(2):1208-1213. doi: 10.1016/j.ygeno.2019.07.006. Epub 2019 Jul 8.

Authors

Ali Yousefian-Jazi¹, Jieun Jung¹, Jung Kyoon Choi², Jinwook Choi³

Affiliations

¹ Interdisciplinary Program, Bioengineering Major, Graduate School, Seoul National University, Seoul 151-742, Republic of Korea.
² Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea.
³ Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul 110-744, Republic of Korea; Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-744, Republic of Korea. Electronic address: jinchoi@snu.ac.kr.

PMID: 31295546
DOI: 10.1016/j.ygeno.2019.07.006

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.

Keywords: Autoimmune diseases; Epigenetics; Genome-wide association study; Random Forest.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dermatitis, Atopic / genetics*
Inflammatory Bowel Diseases / genetics*
Polymorphism, Single Nucleotide*
Regulatory Sequences, Nucleic Acid
STAT3 Transcription Factor / genetics*
Tumor Necrosis Factor-alpha / genetics*

Substances

STAT3 Transcription Factor
STAT3 protein, human
Tumor Necrosis Factor-alpha