Expressive

rs11768410 (SEMA3E): Rosacea Severity Variant

Key takeaways

  • Found in a genome-wide study of 73,265 people as associated with how severe rosacea symptoms are
  • Located near SEMA3E, a gene that guides blood vessel development, which is relevant because rosacea involves persistent facial redness and visible blood vessels
  • Increases SEMA3E expression in thyroid tissue, suggesting this variant regulates gene activity in at least some tissues
  • Evidence is from a single large study with no independent replication yet reported, so findings are preliminary
  • The nearby PCLO gene encodes a large nerve-cell scaffolding protein, but its specific role at this locus in rosacea has not been described in the provided sources

Key takeaways

  • rs11768410 was found in a genome-wide association study linking this chromosomal region to rosacea symptom severity in 73,265 people of European ancestry
  • The locus sits near two genes: PCLO (piccolo, a large scaffolding protein found at synapses, the junctions between nerve cells) and SEMA3E (semaphorin 3E, a member of a family of guidance molecules involved in directing the growth of blood vessels and nerve fibers)
  • In thyroid tissue, this variant is associated with increased SEMA3E expression, suggesting it can influence how much of this protein is produced
  • Rosacea involves abnormal blood vessel behavior in facial skin, and SEMA3E's role as a vascular guidance molecule makes this locus biologically plausible, though a direct mechanistic link has not been demonstrated in the provided sources
  • The rosacea evidence comes from a single large study with no independent replication reported in the provided sources, so findings should be treated as preliminary

What the research says A genome-wide association study of rosacea symptom severity, enrolling 73,265 individuals of European ancestry from the 23andMe research cohort, used a 32-point composite score covering facial, nasal, and ocular symptoms, with analysis adjusted for age, sex, and the first five ancestry principal components. Seven chromosomal loci reached genome-wide significance (p < 5 x 10^-8), and all were described as novel associations except the HLA region, which had been previously reported. Separately, expression quantitative trait locus (eQTL) data from GTEx (a large tissue gene-expression reference resource based on 953 donors) shows that the alternate allele of rs11768410 is associated with increased SEMA3E expression in thyroid tissue, with an effect size of +0.16 in log2-normalized expression units (p = 9.8 x 10^-5) GTEx Portal.

Reported associations

  • Rosacea symptom severity: rs11768410, near PCLO and SEMA3E, was identified in a GWAS of rosacea symptom severity scored on a 32-point composite scale in 73,265 European-ancestry participants from the 23andMe research cohort; specific per-allele effect sizes for this locus were not included in the provided study text
  • SEMA3E expression in thyroid tissue (eQTL): the alternate allele is associated with increased SEMA3E transcript levels in thyroid tissue, with an effect size of +0.16 (log2-normalized, p = 9.8 x 10^-5) GTEx Portal

Evidence quality The rosacea association is supported by a single large genome-wide study of 73,265 European-ancestry participants, using a continuous symptom severity phenotype (the 32-point composite score) rather than a binary case-control design, which provides greater statistical power for detecting associations. The genome-wide significance threshold was p < 5 x 10^-8 and seven loci met this threshold across the study. However, the provided study text does not report specific odds ratios, beta coefficients, or p-values for rs11768410 individually, and no independent replication cohort is described for this locus in the provided sources. All seven genome-wide significant findings were novel except the HLA region, limiting the available cross-study replication evidence. The GTEx eQTL signal for SEMA3E in thyroid is derived from an FDR-controlled analysis across 953 donors GTEx Portal; however, thyroid is not the primary tissue affected in rosacea, and the eQTL observation does not by itself confirm an effect on rosacea symptom severity. Overall, evidence for this locus should be treated as preliminary.

Tissue-specific expression effects

  • SEMA3E: the alternate allele at this locus is associated with increased SEMA3E expression in thyroid tissue; no other tissues showed a significant eQTL effect in the provided data GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11768410?

rs11768410 is a genetic variant located near two genes, PCLO and SEMA3E, that was identified in a genome-wide association study of rosacea symptom severity in over 73,000 people. It may also influence how much SEMA3E protein is produced in certain tissues.

What does SEMA3E do?

SEMA3E, or semaphorin 3E, is a member of the semaphorin family, a group of signaling proteins that act as guidance cues for growing nerve fibers and blood vessels. The connection between SEMA3E and rosacea may relate to the abnormal blood vessel behavior that is a hallmark of the condition.

Is rs11768410 linked to rosacea?

This variant was identified in a genome-wide association study of 73,265 people that measured rosacea symptom severity on a 32-point scale. The finding has not been independently replicated in the provided sources, so the evidence is considered preliminary.

What does the gene expression data show for rs11768410?

Data from GTEx, a large tissue gene-expression reference resource, shows that people carrying the alternate allele of rs11768410 tend to have higher SEMA3E expression in thyroid tissue. This suggests the variant may act as a regulatory switch that increases SEMA3E gene activity, though how this connects to rosacea is not yet established.

What is the PCLO gene?

PCLO, also called piccolo, is a large protein found at synapses, which are the contact points between nerve cells. It helps organize the release of chemical signals between neurons. PCLO sits near rs11768410 in the genome, but the provided research does not describe a specific role for PCLO in rosacea.