rs1032784 (CNTN4): Adipocyte Lipolysis Variant
Key takeaways
- rs1032784 in CNTN4 was one of 60 suggestive loci for fat cell lipolysis in a genome-wide study of 939 adults; it did not cross the threshold for a confirmed genome-wide finding.
- The only genome-wide-significant hit in the same study pointed to HIF3A on chromosome 19, not this locus.
- GTEx data show the alternate allele is associated with reduced expression of a nearby gene (ENSG00000288831) in thyroid tissue.
- Evidence is preliminary: no replication data are available in the provided sources, and functional studies have been conducted only on the separate HIF3A locus.
- No clinical or lifestyle recommendations can be drawn from current evidence.
Key takeaways
- rs1032784 in CNTN4 was one of 60 suggestive loci for fat cell lipolysis in a genome-wide study of 939 adults; it did not cross the threshold for a confirmed genome-wide finding.
- The only genome-wide-significant hit in the same study pointed to HIF3A on chromosome 19, not this locus.
- GTEx data show the alternate allele is associated with reduced expression of a nearby gene (ENSG00000288831) in thyroid tissue.
- Evidence is preliminary: no replication data are available in the provided sources, and functional studies have been conducted only on the separate HIF3A locus.
- No clinical or lifestyle recommendations can be drawn from current evidence.
What the research says A genome-wide association study (GWAS, a scan of genetic variants across the entire genome for links to a trait) of spontaneous and catecholamine-stimulated lipolysis (the breakdown of stored fat into fatty acids) in adipocytes from abdominal subcutaneous fat was conducted in 939 participants from the GENetics of Adipocyte Lipolysis (GENiAL) cohort; 60 loci showed suggestive associations with one or both lipolysis traits, with rs1032784 in the CNTN4 region among those findings. The only locus to reach genome-wide significance (p<5e-8) in that study was on chromosome 19, where HIF3A was identified as the likely causal gene through genotype-dependent expression and in vitro knockdown experiments; this finding is distinct from this locus. Separately, GTEx eQTL (expression quantitative trait locus, a variant that influences how much a nearby gene is expressed) data from 953 donors show the alternate allele of rs1032784 is linked to reduced expression of ENSG00000288831 in thyroid tissue (effect size: -0.17 log2-normalized units, p=7.8e-5, FDR<0.05) GTEx Portal.
Reported associations
- Spontaneous adipocyte lipolysis: Suggestive GWAS association in 939 adults from the GENiAL cohort; exact p-value for this locus is not reported in the provided study text.
- Catecholamine-stimulated adipocyte lipolysis: The GENiAL study noted that many suggestive loci influenced both spontaneous and stimulated lipolysis; overlap at this locus is possible but not confirmed in the available text.
- Thyroid tissue gene expression (ENSG00000288831): The alternate allele is associated with reduced expression in thyroid tissue (GTEx v11, 953 donors, p=7.8e-5) GTEx Portal.
Evidence quality The sole GWAS source linking rs1032784 to lipolysis is the GENiAL study (n=939), which is modest for a genome-wide scan (large GWASs commonly enroll tens of thousands of participants). The association is suggestive only, falling below the conventional p<5e-8 genome-wide significance threshold, and the study's functional work focused exclusively on the chromosome 19 HIF3A locus, leaving this locus without experimental validation in the provided sources. No independent replication cohort is described. The GTEx eQTL signal in thyroid tissue (slope -0.17 log2-normalized units, p=7.8e-5, FDR<0.05, n=953 donors) provides modest support for a regulatory role at this locus, but an eQTL in thyroid tissue does not directly implicate this variant in adipose biology GTEx Portal. Overall, the evidence is preliminary and requires replication before firm conclusions can be drawn.
Tissue-specific expression effects
- ENSG00000288831: Reduced expression in thyroid tissue associated with the alternate allele of rs1032784; no other tissues showed significant eQTL effects in the provided GTEx v11 dataset GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs1032784 and what gene is it in?
rs1032784 is a genetic variant located in the CNTN4 gene. It was identified as one of 60 suggestive loci in a genome-wide study of fat cell lipolysis, the process by which fat cells break down stored triglycerides into fatty acids.
Is rs1032784 linked to fat metabolism or obesity?
A genome-wide study found rs1032784 in CNTN4 was among loci with suggestive association with the rate of lipolysis in fat cells. The association did not reach the conventional threshold for a confirmed genome-wide finding, so evidence remains preliminary and does not establish a confirmed link to obesity.
What does rs1032784 do in thyroid tissue?
GTEx data from 953 donors show the alternate allele of rs1032784 is associated with reduced expression of a nearby gene (ENSG00000288831) in thyroid tissue. The clinical significance of this expression change is not described in the available sources.
How strong is the scientific evidence for rs1032784?
Evidence is weak and preliminary. The only relevant genome-wide study had 939 participants, which is modest for this type of research, and the association at the CNTN4 locus did not reach genome-wide significance. No independent replication study is available in the provided sources.
What is the CNTN4 gene?
The provided studies do not describe the biological function of CNTN4. The gene appears in the context of a lipolysis genome-wide association study, but no functional characterization of this locus was performed in the available research.