Expressive

rs11646791 (MAFTRR): Hypothyroidism Risk Locus

Key takeaways

  • rs11646791 is one of 350 genetic loci linked to hypothyroidism in a genome-wide study covering over 1.1 million individuals
  • The variant maps to MAFTRR, a long non-coding RNA gene that does not produce a protein
  • The alternate allele is consistently associated with reduced MAFTRR expression across seven tissue types including fat, skin, adrenal gland, and colon
  • Evidence for this specific locus comes from one large-scale GWAS; its individual effect size was not reported in available sources

Key takeaways

  • rs11646791 is one of 350 genetic loci linked to hypothyroidism in a genome-wide study covering over 1.1 million individuals
  • The variant maps to MAFTRR, a long non-coding RNA (lncRNA) gene that does not produce a protein
  • The alternate allele is consistently associated with reduced MAFTRR expression across seven tissue types including fat, skin, adrenal gland, and colon
  • Evidence for this specific locus comes from one large-scale GWAS; its individual effect size was not reported in the available study text

What the research says A genome-wide meta-analysis of hypothyroidism identified 350 lead variants across 113,393 cases and 1,065,268 controls from European cohorts, including 179 loci not previously reported, 29 of which were specifically linked through thyroid-stimulating hormone (TSH) genome-wide associations used as prior signals. The analysis also incorporated free thyroxine (fT4, n=191,449) and TSH (n=482,873) data, and gene-mapping strategies prioritized 259 putative causal genes enriched in immune-related functions. Separately, expression quantitative trait locus (eQTL) data show that the alternate allele at this position is associated with reduced MAFTRR lncRNA expression across at least seven tissues and reduced LINC01229 lncRNA expression in liver GTEx Portal.

Reported associations

  • Hypothyroidism: identified as one of 350 genome-wide significant loci in a meta-analysis of 113,393 cases and 1,065,268 European-ancestry controls; a specific odds ratio for this variant was not reported in the available text
  • Thyroid-stimulating hormone (TSH): 29 of the 179 newly identified hypothyroidism loci were specifically linked through TSH genome-wide associations used as priors; whether rs11646791 falls in this subset is not specified in the available text
  • MAFTRR expression (multi-tissue eQTL): the alternate allele is associated with reduced MAFTRR lncRNA expression across seven tissues with effect slopes ranging from -0.43 to -0.69 (all FDR<0.05, GTEx v11, n=953 donors) GTEx Portal
  • LINC01229 expression (liver eQTL): the alternate allele is associated with reduced LINC01229 lncRNA expression in liver tissue (slope approximately -0.70, p=2.3e-28) GTEx Portal

Evidence quality The hypothyroidism GWAS meta-analysis combined data from the Copenhagen Hospital Biobank and Danish Blood Donor Study (CHB-CID/DBDS), UK Biobank, FinnGen, and 23andMe, representing one of the largest thyroid disease genetics studies to date (113,393 cases, 1,065,268 controls). The genomic inflation factor (lambda-GC) of 1.46 reflects the large sample size rather than systematic analytical bias. rs11646791 is listed as one of the 350 lead variants, but its individual p-value, odds ratio, or replication status in an independent cohort are not available in the provided text. The GTEx eQTL associations for MAFTRR are derived from GTEx v11 (953 donors, FDR<0.05) and show a consistent direction of reduced expression across all seven tissues tested. No conflicting GWAS or eQTL findings are present in the provided sources. Evidence linking this specific locus to a functional mechanism in thyroid biology remains preliminary.

Tissue-specific expression effects

  • MAFTRR: the alternate allele is associated with reduced expression in testis, adrenal gland, transverse colon, subcutaneous adipose tissue, visceral (omental) adipose tissue, non-sun-exposed skin, and sun-exposed skin, a consistent pattern of decreased lncRNA levels across metabolically and hormonally relevant tissues GTEx Portal
  • LINC01229: the alternate allele is associated with reduced expression specifically in liver tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11646791?

rs11646791 is a single-nucleotide genetic variant located near MAFTRR, a long non-coding RNA gene. It was identified as one of 350 loci associated with hypothyroidism in a large genome-wide association study of over 1.1 million individuals.

What is MAFTRR and what does it do?

MAFTRR (MAF Transcriptional Regulator RNA) is a long non-coding RNA, meaning it is an RNA molecule that does not produce a protein but may play a role in regulating other genes. Its specific function in thyroid biology has not yet been fully characterized in the available research.

Is rs11646791 linked to thyroid disease?

It was identified as a genome-wide significant locus for hypothyroidism in a meta-analysis of 113,393 cases and over one million controls. The specific effect size for this individual variant was not reported in the available study text.

Which tissues does rs11646791 affect gene expression in?

According to GTEx v11 data, the alternate allele is associated with reduced MAFTRR expression in testis, adrenal gland, transverse colon, subcutaneous fat, visceral fat, and two skin tissue types. It is also linked to reduced LINC01229 expression in liver.

What is a long non-coding RNA?

A long non-coding RNA (lncRNA) is an RNA molecule longer than 200 nucleotides that does not encode a protein. LncRNAs can influence how other genes are expressed, but their functions are often less well understood than those of protein-coding genes.