ArticleHuman genetics2015
Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1.
Article in Human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Article
- Genetic aspects of pediatric nephrotic syndrome and anti-nephrin antibodies.Clinical and experimental nephrology · 2025Review
- rs10924104 in the expression enhancer motif of CD58 confers susceptibility to human autoimmune diseases.Human genetics · 2024Article
- Review
- rs2013278 in the multiple immunological-trait susceptibility locus CD28 regulates the production of non-functional splicing isoforms.Human genomics · 2022Article
- An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2022Review
- Novel insights in the genetics of steroid-sensitive nephrotic syndrome in childhood.Pediatric nephrology (Berlin, Germany) · 2021Review
- Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.Kidney international · 2020Article
- [Advances in the study of abnormal expression of genes related to primary biliary cholangitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2019Article
- POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33.Scientific reports · 2019Article
- NFKB1 and MANBA Confer Disease Susceptibility to Primary Biliary Cholangitis via Independent Putative Primary Functional Variants.Cellular and molecular gastroenterology and hepatology · 2019Article
- Role ofWorld journal of gastrointestinal pathophysiology · 2018Article
- Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis.Scientific reports · 2017Article
- A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.Nature communications · 2017Article
- Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2017Review
- Distinct functional enrichment of transcriptional signatures in pigs with high and low IFN-gamma responses after vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV).Veterinary research · 2016Article
- Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy.Scientific reports · 2016Article
- Association of IL12A Expression Quantitative Trait Loci (eQTL) With Primary Biliary Cirrhosis in a Chinese Han Population.Medicine · 2016Article
- The immunogenetics of primary biliary cirrhosis: A comprehensive review.Journal of autoimmunity · 2015Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A genome-wide association study (GWAS) identified tumor necrosis factor superfamily member 15 (TNFSF15) as the strongest associated gene with susceptibility to primary biliary cirrhosis (PBC) outside the HLA loci in the Japanese population. However, causal functional variants of the TNFSF15 locus and the molecular mechanism underlying disease susceptibility have not been clarified. Here, to identify the functional causal variants of the TNFSF15 locus, integrated analysis comprising in silico analysis, a case-control association study and in vitro functional analysis was performed. Initially, 32 functional candidate single-nucleotide polymorphisms (SNPs) in the expression regulatory motifs, the coding region, or the untranslated regions (UTRs) of the TNFSF15 locus were selected by in silico analysis. By the case-control association studies using PBC patients (n = 1279) and healthy controls (n = 1091) in the Japanese population, rs4979462 [P = 1.85 × 10(-14) (our previous study)], rs56211063 (P = 2.21 × 10(-14)), and rs55768522 (r(2) = 1 with rs4979462) were likely candidates for causal variants. Among these SNPs, rs4979462 was identified as the causal variant by in vitro functional analysis using luciferase assay and electrophoretic mobility shift assay (EMSA). Super-shift assay clarified that PBC-susceptible allele of rs4979462 generated a novel NF-1 binding site. Moreover, higher endogenous TNFSF15 protein and mRNA expression levels were observed in individuals with the PBC-susceptible allele of rs4979462. This study identified the causal variant for PBC susceptibility in the TNFSF15 locus and clarified its underlying molecular mechanism. TNFSF15 and NF-1 are considered to be potential targets for the treatment of PBC.
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