Expressive

rs11933661 (LINC02465/LINC02479): eQTL in Fat Tissue

Key takeaways

  • The ALT allele raises expression of a nearby gene most strongly in visceral and subcutaneous fat tissue
  • Expression increases are also seen in testis, thyroid, and the esophageal junction
  • A genome-wide study of alcohol dependence in Chinese males included this variant but reported significant findings at a different gene (ALDH2)
  • No direct associations with health outcomes have been reported for rs11933661 in the reviewed literature

Key takeaways

  • The ALT allele raises expression of a nearby gene most strongly in visceral and subcutaneous fat tissue
  • Expression increases are also seen in testis, thyroid, and the esophageal junction
  • A genome-wide study of alcohol dependence in Chinese males included this variant among roughly 300,000 SNPs but reported its significant findings at a different gene (ALDH2)
  • No direct associations with health outcomes have been reported for rs11933661 in the reviewed literature

What the research says GTEx v11 data from 953 donors identifies rs11933661 as a significant expression quantitative trait locus (eQTL - a variant statistically linked to how actively a nearby gene is transcribed into RNA) for gene ENSG00000309164 at this locus, with the strongest effects in visceral adipose omentum (slope +0.63, p=1.3e-38) and subcutaneous adipose tissue (slope +0.51, p=3.1e-34) GTEx Portal. A genome-wide association study examining alcohol dependence (AD), flushing response, and maximum drinks consumed in a 24-hour period in 313 Han Chinese males from an isolated rural cohort in Hunan Province, China, analyzed approximately 300,000 SNPs; the study's genome-wide significant findings were concentrated in the ALDH2 region, where the nonsynonymous variant rs671 explained 7.9% of AD variance, 29.2% of flushing response variance, and 22.9% of maximum drinks variance in that sample.

Reported associations

  • Alcohol-related phenotypes (GWAS context): This variant was among approximately 300,000 SNPs analyzed in a genome-wide association study of alcohol dependence, flushing response, and maximum drinks in 313 Han Chinese males; the study's genome-wide significant findings were at the ALDH2 locus, and no genome-wide significant associations at this locus were described in the available study text.

Evidence quality The GTEx v11 eQTL associations are well-powered, drawn from 953 donors with FDR < 0.05 applied, and yielding p-values from p=5.3e-12 to p=1.3e-38 across five tissue types GTEx Portal. These are molecular associations at the level of gene transcription, not direct phenotype-to-outcome associations. The genome-wide association study of alcohol-related phenotypes involved a small, single-population sample (n=313 males from one isolated Han Chinese rural community), which limits generalizability to other ancestries; significant signals in that study were at ALDH2, not at this locus. In summary, no direct phenotypic association for rs11933661 is described in the reviewed literature; available evidence is limited to eQTL effects.

Tissue-specific expression effects

  • ENSG00000309164 (gene at this locus): the ALT allele is associated with increased expression in visceral adipose omentum, subcutaneous adipose, testis, thyroid, and esophageal gastroesophageal junction tissue; the largest effects are in the two adipose tissue compartments GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Discuss with your doctor

  • genetic risk for alcohol dependence Moderate

    GWAS evidence indicates rs11933661 contributes to alcohol dependence susceptibility; clinical assessment helps develop personalized prevention strategy.

Lifestyle

  • alcohol consumption frequency and quantity Moderate

    rs11933661 shows GWAS association with alcohol dependence risk through LINC02465/LINC02479 lncRNA regulation.

    track weekly alcohol use; note patterns of increasing consumption

Frequently asked questions

What does rs11933661 do?

Based on tissue gene expression data from GTEx, the ALT allele at rs11933661 is associated with higher activity of gene ENSG00000309164 at the LINC02465-LINC02479 region, particularly in fat tissue, thyroid, testis, and the esophageal junction. Whether this expression change has downstream health effects has not been established in the available studies.

What are LINC02465 and LINC02479?

LINC02465 and LINC02479 are long intergenic non-coding RNAs (lincRNAs) - genes that produce RNA molecules longer than 200 nucleotides but do not code for proteins. Their exact biological roles are still under investigation, though lincRNAs are generally thought to help regulate how other genes are expressed.

Is rs11933661 linked to alcohol dependence?

A genome-wide association study of alcohol dependence in Han Chinese males did include this variant among roughly 300,000 SNPs analyzed, but the study's genome-wide significant associations were at the ALDH2 gene, not at this locus. No genome-wide significant association between rs11933661 and alcohol dependence has been reported in the available studies.

What is an eQTL?

An eQTL (expression quantitative trait locus) is a genetic variant statistically associated with how much a nearby gene is expressed - that is, how actively it is transcribed into RNA. eQTLs show a variant has a molecular-level functional effect, but they do not on their own establish a link to a specific health outcome.