Expressive

rs12035082 (TNFSF18): Crohn Disease Gene Desert Locus

Key takeaways

  • rs12035082 lies in a chromosome 1q region flagged as a gene desert in Crohn disease genome-wide research
  • The alternate allele reduces TNFSF18 expression in subcutaneous fat and lung tissue
  • Four nearby genes or gene sequences show reduced expression across esophageal, skin, adipose, and heart tissues
  • The Crohn disease link comes from a combined analysis of over 7,000 individuals, but per-variant data for rs12035082 are not directly reported
  • No drug-response or lifestyle data are on file for this variant

Key takeaways

  • rs12035082 lies in a chromosome 1q region - containing TNFSF18 (tumor necrosis factor superfamily member 18) and AIMP1P2 - that was flagged as a gene desert in Crohn disease genome-wide research
  • The alternate allele reduces TNFSF18 expression in subcutaneous fat and lung tissue
  • Four nearby genes or gene sequences show reduced expression across esophageal, skin, adipose, and heart tissues
  • The Crohn disease link comes from a combined analysis of over 7,000 individuals, but per-variant data for rs12035082 are not directly reported in the available study text
  • No drug-response or lifestyle data are on file for this variant

What the research says

A replication analysis of Wellcome Trust Case Control Consortium (WTCCC) Crohn disease data, combining 2,930 cases and 4,962 controls, identified multiple novel susceptibility loci including gene deserts on chromosomes 1q and 5p13 - the 1q region being the chromosomal location of TNFSF18 and AIMP1P2. GTEx v11 data from 953 donors show the alternate allele of rs12035082 reduces TNFSF18 expression in subcutaneous adipose tissue (p=1.9e-6) and lung (p=8.8e-5), both FDR<0.05 GTEx Portal. The same allele reduces expression of the nearby pseudogene sequence ENSG00000224000 across four tissue contexts - esophagus muscularis, two skin subtypes, and subcutaneous fat - with p-values ranging from 1.1e-8 to 6.9e-7, all FDR<0.05 GTEx Portal.

Reported associations

  • Crohn disease: The chromosome 1q gene desert covering this region was listed among replicated loci in a combined Crohn disease case-control panel of 2,930 cases and 4,962 controls; the source study does not report per-variant statistics for rs12035082.
  • TNFSF18 expression (subcutaneous adipose): Reduced expression associated with the alternate allele (p=1.9e-6, FDR<0.05, n=953 donors) GTEx Portal.
  • TNFSF18 expression (lung): Reduced expression associated with the alternate allele (p=8.8e-5, FDR<0.05) GTEx Portal.
  • ENSG00000224000 expression (AIMP1P2 region pseudogene): Reduced expression in esophagus muscularis (p=6.2e-7), non-sun-exposed skin (p=9.1e-8), sun-exposed skin (p=1.1e-8), and subcutaneous adipose tissue (p=6.9e-7), all FDR<0.05 GTEx Portal.
  • ENSG00000301437 expression (heart atrial appendage): Reduced expression (p=7.5e-6, FDR<0.05) GTEx Portal.
  • ENSG00000226375 expression (esophagus muscularis): Reduced expression (p=1.6e-5, FDR<0.05) GTEx Portal.

Evidence quality

The Crohn disease connection for this variant is indirect: the source study's abstract notes that gene deserts on chromosomes 1q and 5p13 were among replicated loci in a combined panel of 2,930 cases and 4,962 controls, but the detailed text does not report association data for the 1q locus or name rs12035082. The overall study drew on WTCCC discovery data (1,748 cases and 2,938 controls genotyped on the Affymetrix 500K chip) plus an independent cohort of 1,182 Caucasian cases and 2,024 population controls from the 1958 British Birth Cohort. GTEx eQTL data are derived from 953 donors with FDR<0.05 applied; TNFSF18 expression signals are consistent across two tissues, and ENSG00000224000 signals replicate across four tissues with p-values as strong as 1.1e-8, lending modest confidence to those specific associations. No independent replication of any eQTL signal for rs12035082 is reported in the provided materials, and no clinical outcome data are linked to the expression changes documented here. The overall body of evidence for this variant is preliminary.

Tissue-specific expression effects

  • ENSG00000224000 (AIMP1P2 region pseudogene): The alternate allele is associated with reduced expression in esophagus muscularis, non-sun-exposed skin, sun-exposed skin, and subcutaneous adipose tissue GTEx Portal.
  • TNFSF18: The alternate allele is associated with reduced expression in subcutaneous adipose tissue and lung GTEx Portal.
  • ENSG00000301437: The alternate allele is associated with reduced expression in heart atrial appendage tissue GTEx Portal.
  • ENSG00000226375: The alternate allele is associated with reduced expression in esophagus muscularis GTEx Portal.

Lifestyle considerations

No lifestyle considerations on file for this variant.

Frequently asked questions

What is TNFSF18?

TNFSF18 is a protein in the tumor necrosis factor superfamily involved in immune system signaling. It plays a role in regulating immune cell activity and has been studied in the context of inflammatory conditions.

Is rs12035082 linked to Crohn disease?

A chromosome 1q gene desert region near rs12035082 was listed among replicated loci in Crohn disease genome-wide research combining data from over 7,000 individuals. However, per-variant statistics for rs12035082 itself are not reported in the available study text, so the connection is indirect and based on regional overlap.

What does rs12035082 do to gene expression?

According to GTEx v11 data from 953 donors, the alternate allele reduces TNFSF18 expression in fat and lung tissue. It also reduces expression of the AIMP1P2 pseudogene region across esophagus, skin, and fat, and two other nearby gene sequences in esophagus and heart tissue.

What is the AIMP1P2 pseudogene?

AIMP1P2 is a pseudogene - a DNA sequence resembling a protein-coding gene but not producing a functional protein - located near TNFSF18 on chromosome 1q. GTEx data show that rs12035082 affects expression of a pseudogene sequence in this region across multiple tissues.

Is rs12035082 relevant to inflammatory bowel disease?

The chromosomal region near rs12035082 was flagged in Crohn disease research, which is one form of inflammatory bowel disease. Direct association data for this specific variant are limited, and its role in inflammatory bowel disease has not been independently confirmed in the provided literature.