Expressive

rs12206866 (LINC02532): Immune Cell Variant

Key takeaways

  • rs12206866 sits in LINC02532, a non-coding RNA locus, and was found in a Sardinian GWAS of 3,757 people scanning 731 immune cell traits.
  • The study found 122 significant genetic signals for immune cell variation, with 53 overlapping known autoimmune disease risk loci.
  • GTEx data show the alternate allele is linked to reduced CD24 expression in the spleen.
  • The same allele is linked to higher QRSL1 expression in thyroid and skin, and higher MTRES1 expression in heart tissue.
  • Findings come from a single-ancestry Sardinian cohort and have not been confirmed in independent populations.

Key takeaways

  • rs12206866 sits in LINC02532, a long intergenic non-coding RNA locus, and was studied in a large genome-wide analysis of immune cell traits in a Sardinian cohort.
  • The GWAS screened approximately 22 million variants across 731 immune cell measurements in 3,757 participants, finding 122 significant independent association signals for 459 traits at 70 loci.
  • GTEx eQTL data link the alternate allele to reduced CD24 expression in the spleen and increased QRSL1 and MTRES1 expression in thyroid, skin, and heart tissue.
  • Fifty-three of the study's association signals overlapped with known autoimmune disease risk loci, identifying candidate immune cell intermediate phenotypes.
  • Evidence is limited to a single-ancestry Sardinian cohort with no documented replication in independent populations.

What the research says A genome-wide association study in 3,757 Sardinians tested approximately 22 million genetic variants across 731 immune cell traits (including absolute cell counts, surface antigen expression levels measured by median fluorescence intensity, and morphological parameters) and identified 122 significant independent association signals (P < 1.28 x 10^-11) for 459 cell traits at 70 loci, 53 of them novel. Of those signals, 53 at 36 loci overlapped with previously reported disease-associated variants, predominantly for autoimmune conditions, pointing to immune cell measurements as candidate intermediate phenotypes in pathogenesis. GTEx eQTL data from 953 donors (FDR < 0.05) show the alternate allele of rs12206866 is associated with reduced CD24 expression in the spleen (slope -0.35, p=8.5e-5), increased QRSL1 expression in thyroid and skin, and increased MTRES1 expression in the heart atrial appendage GTEx Portal.

Reported associations

  • Immune cell traits (GWAS): rs12206866 was studied in a Sardinian GWAS that detected 122 significant signals across 459 immune cell phenotypes (counts, surface antigen levels, and cell ratios) in 3,757 participants; specific per-variant effect sizes for this rsid at individual immune traits are not detailed in the provided study excerpt.
  • Autoimmune disease overlap: The source GWAS found 53 of its association signals at 36 loci overlapping with known autoimmune disease risk variants, identifying candidate immune cell intermediate phenotypes in pathogenesis; whether this specific locus is among those 36 is not confirmed in the available study text.
  • CD24 expression - Spleen (eQTL): The alternate allele is associated with reduced CD24 expression in spleen tissue (slope -0.35, p=8.5e-5) GTEx Portal.
  • QRSL1 expression - Thyroid and Skin (eQTL): The alternate allele is associated with increased QRSL1 expression in thyroid tissue (slope +0.31, p=1.1e-4) and sun-exposed lower leg skin (slope +0.30, p=1.8e-4) GTEx Portal.
  • MTRES1 expression - Heart (eQTL): The alternate allele is associated with increased MTRES1 expression in the heart atrial appendage (slope +0.21, p=6.5e-5) GTEx Portal.

Evidence quality The primary immune cell GWAS used a cohort of 3,757 Sardinians genotyped at approximately 22 million variants, with a stringent significance threshold of P < 1.28 x 10^-11 applied across 731 immune traits. The Sardinian founder population offers enhanced statistical power for local variant discovery but limits generalizability to other ancestries. Specific effect sizes for this variant at individual immune cell traits are not available in the provided study text. GTEx eQTL data (953 donors, FDR < 0.05) provide functional tissue-specific context for the variant's regulatory role, though eQTL associations reflect gene regulation mechanisms rather than direct clinical outcomes. Independent replication of immune cell trait associations for this specific variant in non-Sardinian cohorts is not documented in the materials provided, and these findings should be treated as preliminary.

Tissue-specific expression effects

  • CD24: The alternate allele is associated with reduced expression in the spleen (slope -0.35, p=8.5e-5) GTEx Portal.
  • QRSL1: The alternate allele is associated with increased expression in thyroid tissue (slope +0.31, p=1.1e-4) and sun-exposed lower leg skin (slope +0.30, p=1.8e-4) GTEx Portal.
  • MTRES1: The alternate allele is associated with increased expression in the heart atrial appendage (slope +0.21, p=6.5e-5) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs12206866?

rs12206866 is a single-nucleotide variant (a one-letter change in DNA) located in LINC02532, a region encoding a long intergenic non-coding RNA. It was studied in a genome-wide analysis of 731 immune cell traits across 3,757 Sardinian participants.

What does LINC02532 do?

LINC02532 encodes a long intergenic non-coding RNA, a type of RNA that does not produce a protein and may play a regulatory role in gene expression. Its precise biological function is not described in the available research.

Is rs12206866 linked to autoimmune disease?

The study that examined this variant found that 53 of its genome-wide signals overlapped with known autoimmune disease risk loci, pointing to immune cell traits as potential intermediate phenotypes. Whether this specific locus is among those 53 is not confirmed in the available study text.

What does the eQTL data mean for this variant?

An eQTL (expression quantitative trait locus) result means the variant influences how much of a gene is produced in a specific tissue. GTEx data show rs12206866 is linked to lower CD24 levels in the spleen and higher QRSL1 and MTRES1 levels in thyroid, skin, and heart tissue, pointing to a potential regulatory role. These are mechanistic findings and do not directly predict clinical outcomes.

Has this variant been studied in populations outside Sardinia?

The primary GWAS was conducted exclusively in Sardinians, a founder population with distinct genetic characteristics that enhances local discovery power. Independent replication in other ancestries is not documented in the materials provided.