Expressive

rs10282458 (RARRES2): LRRC61 Expression and BMI

Key takeaways

  • rs10282458, near RARRES2-REPIN1-AS1, is connected to protein-level variation in obesity research
  • The alternate allele consistently increases LRRC61 expression across brain, muscle, thyroid, and other tissues
  • A pQTL study in 494 obese individuals found BMI-linked protein variants before and after dietary weight loss
  • Evidence for this specific variant is preliminary, with stronger support from eQTL data than from intervention studies

Key takeaways

  • rs10282458, near the RARRES2-REPIN1-AS1 locus, is connected to protein-level variation in obesity research
  • The alternate allele at this variant consistently increases expression of LRRC61 across brain, muscle, thyroid, and other tissues
  • A protein quantitative trait locus study in 494 obese individuals identified BMI-linked protein variants both before and after a dietary weight-loss intervention
  • Evidence for this specific variant is preliminary, with stronger support from eQTL data than from intervention cohort findings

What the research says A protein quantitative trait locus (pQTL) study - meaning an analysis of how genetic variants influence measured protein levels in the body - was conducted in 494 obese participants from the DIOGenes dietary intervention trial, identifying 55 BMI-associated cis-pQTLs and trans-pQTLs at baseline and 3 trans-pQTLs after a low-calorie diet, and identifying FAM46A as a trans regulator of leptin in adipocytes (fat cells); the specific contribution of rs10282458 to those findings is not detailed in available text. Separately, GTEx v11 eQTL data from 953 donors show that the alternate allele at this locus is associated with increased expression of LRRC61 across at least eight tissue types, with particularly strong effects in brain regions and skeletal muscle GTEx Portal.

Reported associations

  • BMI-associated protein levels (obesity): A pQTL study in obese individuals found genetic variants linked to BMI-associated protein levels at baseline and during a weight-loss intervention, with evidence for distinct genetic mechanisms before and after weight loss; the direct association of rs10282458 with any specific protein is not stated in available text
  • LRRC61 gene expression (eQTL): The alternate allele is associated with increased LRRC61 expression in brain cerebellum (slope +1.08, p=4.3e-40), cerebellar hemisphere (slope +0.95, p=4.0e-45), nucleus accumbens basal ganglia (slope +0.91, p=2.3e-42), skeletal muscle (slope +0.85, p=1.5e-85), testis (slope +0.77, p=5.3e-65), cultured fibroblasts (slope +0.73, p=3.9e-65), esophagus mucosa (slope +0.63, p=6.3e-73), and thyroid (slope +0.56, p=1.2e-85) GTEx Portal

Evidence quality The pQTL study contributing to this entry enrolled 494 obese participants in a single dietary intervention cohort; no PMID is available for this publication, and independent replication of its pQTL findings is not reported in available text, making those associations for this locus preliminary. The GTEx eQTL data are drawn from 953 donors under strict FDR control (FDR < 0.05), and the LRRC61 associations reach highly significant p-values (as low as p=1.5e-85 in skeletal muscle and p=1.2e-85 in thyroid), lending considerably more confidence to the expression-level data than to the obesity intervention findings GTEx Portal. No conflicting findings were present across the provided sources.

Tissue-specific expression effects

  • LRRC61: Increased expression associated with the alternate allele across at least eight tissues, most strongly in brain regions (cerebellum, cerebellar hemisphere, and nucleus accumbens basal ganglia) and also present in skeletal muscle, testis, cultured fibroblasts, esophagus mucosa, and thyroid GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10282458?

rs10282458 is a common genetic variant located near the RARRES2 and REPIN1-AS1 genes. It has been studied for its effects on protein levels in obesity research and its influence on expression of the nearby LRRC61 gene across multiple tissues.

What does the RARRES2 gene do?

RARRES2 encodes a protein involved in metabolic and immune signaling. Variants in this region, including rs10282458, have been examined in studies of obesity-related protein-level traits and tissue-specific gene expression.

What is LRRC61 and how is it connected to rs10282458?

LRRC61 is a gene whose expression level is influenced by the rs10282458 variant according to large-scale GTEx eQTL data from 953 donors. The alternate allele at this position is associated with higher LRRC61 expression in at least eight tissues including brain regions, skeletal muscle, and thyroid.

Is rs10282458 linked to obesity?

A protein quantitative trait locus study in 494 obese participants found BMI-associated protein variants in this genomic area, but the specific role of rs10282458 within those findings is not fully described in available published text. The evidence is preliminary.

What is a protein quantitative trait locus study?

A protein quantitative trait locus (pQTL) study examines how genetic variants influence measured protein levels in blood or tissue. This approach can reveal how genes translate into biological differences, and is particularly useful for understanding metabolic conditions like obesity.