rs3810936

This is a synonymous variant in the TNFSF15 gene — it does not change the protein's amino acid sequence.

GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

Crohn's disease

Allele C
OR 1.21
p 1.0e-15
N 21,389
Meta-analysisLarge GWAS
European

Research that mentions this SNP (4)

TL1A (TNFSF15) genotype affects the long‐term therapeutic outcomes of anti‐TNFα antibodies for Crohn's disease patients
AssociationN=119Katsuya Endo et al.(2020)· JGH Open

This retrospective cohort study investigated 119 Japanese Crohn's disease patients to examine whether TL1A (TNFSF15) genotype affects therapeutic outcomes with anti-TNF antibodies (infliximab and adalimumab). The TL1A -358C/C risk allele (rs6478109) was significantly associated with reduced surgery-free survival (HR 4.67, P = 0.025), with patients homozygous for the risk allele showing lower surgical-free survival compared to those carrying protective alleles. No significant differences were found in drug retention or relapse-free survival between genotypes.

Traits studied:Crohn's diseaseResponse to anti-TNF therapySurgery-free survival in Crohn's disease
Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1
AssociationN=2,370Yuki Hitomi et al.(2015)· Human Genetics

This study identified rs4979462 in the TNFSF15 locus as the causal variant for primary biliary cirrhosis (PBC) susceptibility in the Japanese population through integrated analysis including case-control association (n=1279 PBC cases, n=1091 controls; P=1.85×10⁻¹⁴, OR=1.57) and in vitro functional studies. The PBC-susceptible allele generates a novel NF-1 transcription factor binding site, enhancing TNFSF15 expression and increasing susceptibility to autoimmune liver disease.

Traits studied:Ankylosing spondylitisCrohn's diseaseLeprosyPrimary biliary cirrhosisUlcerative colitis
Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population
AssociationN=7,457Maarit Lappalainen et al.(2008)· Inflammatory Bowel Diseases

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

Traits studied:Acute anterior uveitis (AAU)Ankylosing spondylitis (AS)Spondyloarthropathies
TNFSF15 is an ethnic-specific IBD gene
AssociationN=1,211Yoana Picornell et al.(2007)· Inflammatory Bowel Diseases

TNFSF15 is confirmed as an IBD susceptibility gene showing ethnic-specific associations in a Caucasian population. The protective Haplotype B (OR=0.64, p=0.01 in CD; OR=0.59, p=0.01 in UC) was significantly associated with disease protection in non-Jewish controls but showed opposite frequency trends in Jewish populations (p=0.04 for gene-ethnicity interaction in CD), demonstrating disease susceptibility is ethnically determined.

Traits studied:Crohn's Disease (CD)Inflammatory Bowel Disease (IBD)Ulcerative Colitis (UC)

About TNFSF15

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

View all TNFSF15 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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