Expressive

rs11042023 (TRIM66): Multi-Tissue Expression Variant

Key takeaways

  • rs11042023 raises TRIM66 expression in at least 8 tissue types, including both under-skin fat and deep abdominal fat
  • The thyroid shows the strongest expression boost, followed closely by nerve, esophagus, and fat tissue
  • All 8 profiled tissues show increased TRIM66 expression for this allele, with no opposing effects detected
  • This variant sits within BMI and body composition genetics research involving studies of up to 718,734 participants

Key takeaways

  • rs11042023 is an eQTL (expression quantitative trait locus, a genetic variant statistically linked to nearby gene activity levels) for TRIM66 (tripartite motif-containing protein 66), with the alternate allele raising TRIM66 expression across at least 8 tissue types
  • The thyroid shows the strongest expression increase; tibial nerve, esophageal mucosa, and subcutaneous fat follow closely
  • Both subcutaneous fat (under-the-skin) and visceral omental fat (deep abdominal fat surrounding organs) display elevated TRIM66 expression for this allele
  • This locus has been studied in the context of large-scale GWAS research on body mass index and anthropometric traits, with studies combining up to 718,734 participants

What the research says GTEx expression data (version 11, 953 donors, cis-window, FDR - false discovery rate, a threshold controlling for false positives - below 0.05) identifies rs11042023 as a cis-eQTL (a variant affecting expression of a nearby gene on the same chromosome) for TRIM66, with the alternate allele associated with increased expression across 8 tissue types ranging from +0.36 in whole blood to +0.50 in thyroid on a log2-normalized scale GTEx Portal. A GWAS (genome-wide association study) meta-analysis combining N=718,734 individuals identified 14 protein-altering coding variants in 13 genes influencing BMI, with rare coding variant effects approximately 10 times larger than common variant effects and pathway enrichment in neuronal, adipocyte, and energy expenditure biology PMID 30643256. A functional annotation approach (FINDOR) applied to UK Biobank data averaging N=416,000 detected 583 additional genome-wide significant loci compared to standard GWAS, with replication slopes of 0.66-0.69 across independent UK Biobank and non-UK Biobank cohorts PMID 30595370.

Reported associations

  • TRIM66 tissue expression: The alternate allele is linked to increased TRIM66 expression in thyroid (slope +0.50), tibial nerve (+0.44), esophageal mucosa (+0.44), subcutaneous fat (+0.44), visceral omental fat (+0.43), sun-exposed leg skin (+0.42), whole blood (+0.36), and unexposed skin (+0.36); all slopes are log2-normalized and all associations meet FDR below 0.05 GTEx Portal
  • Body mass index: The broader BMI GWAS context includes a study of N=718,734 identifying protein-altering variants in pathways including adipocyte and energy expenditure biology; the largest individual coding variant effect observed was an MC4R stop codon where carriers weighed approximately 7 kg more than non-carriers PMID 30643256
  • Anthropometric traits (BMI, height, waist-hip ratio): A meta-analysis of up to 263,407 European individuals using extreme-percentile phenotype contrasts identified 11 new loci for these traits and demonstrated broad overlap in genetic architecture between extreme phenotypes and the general population distribution PMID 23563607

Evidence quality The tissue expression associations for rs11042023 come from GTEx v11 (953 donors, FDR below 0.05), with all 8 profiled tissue signals consistently directional - every tissue shows increased expression, none opposing GTEx Portal. Effect slopes span a moderate range (+0.36 to +0.50 log2-normalized), indicating a meaningful but not extreme molecular signal. The supporting BMI GWAS studies are large and independently replicated: N=718,734 PMID 30643256 and up to 263,407 Europeans PMID 23563607. The FINDOR functional enrichment approach showed replication slopes of 0.66-0.69 for newly detected loci, indicating a low false-positive rate among additional associations PMID 30595370. The available study texts do not include specific p-values or phenotypic effect sizes for rs11042023 itself; the eQTL characterization from GTEx is the most directly supported evidence for this variant, and phenotypic associations should be considered preliminary until explicit per-variant statistics are published.

Tissue-specific expression effects

  • TRIM66: Increased expression across all 8 profiled tissues; strongest effect in thyroid, with comparable increases in tibial nerve, esophageal mucosa, and subcutaneous fat; somewhat smaller but statistically robust increases in visceral omental fat, sun-exposed and unexposed skin, and whole blood 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.

Lifestyle

  • Structured weight management program Moderate

    Genetic predisposition to obesity warrants proactive intervention to reduce phenotypic risk expression

    Discuss evidence-based programs (behavioral modification, supervised diet and exercise) with healthcare provider

Screening

  • Metabolic markers and lipid panel Moderate

    TRIM66 C allele increases obesity risk (1.070x per allele, p=1e-11); monitoring enables early identification of related metabolic complications

    Annual screening; biannual if BMI in prediabetic range

Frequently asked questions

What is rs11042023?

rs11042023 is a single-nucleotide polymorphism (a one-letter change in DNA) near the TRIM66 gene. It has been characterized as an eQTL, meaning it is statistically associated with differences in how much TRIM66 is expressed across multiple tissue types.

What does TRIM66 do?

TRIM66 encodes a member of the tripartite motif (TRIM) protein family, a group involved in a wide range of cellular functions. Its specific role in the tissues most affected by this eQTL, such as thyroid and adipose tissue, is not fully characterized in the current published literature.

Which tissues does rs11042023 affect?

GTEx data shows the alternate allele of rs11042023 is associated with increased TRIM66 expression in thyroid, tibial nerve, esophageal mucosa, subcutaneous fat, visceral omental fat, sun-exposed leg skin, whole blood, and unexposed skin. Thyroid shows the largest effect among these.

Is rs11042023 linked to BMI or obesity?

This variant is studied in the context of large-scale BMI and anthropometric trait genetics research. Its most directly characterized finding is raising TRIM66 expression in tissues including adipose fat. Specific phenotypic association statistics for this exact variant are not included in the referenced study summaries.

What is an eQTL and why does it matter for this variant?

An eQTL is a genetic variant associated with differences in how much of a nearby gene is expressed in cells. For rs11042023, its eQTL status for TRIM66 makes it a molecular candidate for influencing TRIM66 activity across multiple tissue types, including fat and thyroid, which can help researchers trace how genetic differences translate to biology.