Expressive

rs11074889 (EMP2): Tissue Expression & ADHD

Key takeaways

  • rs11074889 raises EMP2 gene activity most strongly in the pancreas, with additional effects in blood vessels, nerves, and skin
  • The same variant reduces activity of two nearby genes, ENSG00000279662 in sun-exposed skin and LINC01290 in unexposed skin and lung
  • This locus appeared in a family-based ADHD genome-wide scan of 735 trios, but no significant association was reported at this position
  • Gene-expression data from GTEx (953 donors) provides the most robust evidence for this variant, with several tissue signals reaching p-values below 1E-9
  • No lifestyle or drug-response data for this variant was identified in the provided materials

Key takeaways

  • rs11074889 is a variant near EMP2 (Epithelial Membrane Protein 2) that raises EMP2 gene activity most strongly in the pancreas, with additional effects in blood vessels, nerves, and skin
  • The same variant also reduces activity of two nearby genomic elements, ENSG00000279662 in sun-exposed skin and LINC01290 in unexposed skin and lung
  • This locus was included in a family-based GWAS of ADHD involving 735 trios, but no genome-wide significant association was reported
  • Gene-expression (eQTL) data from GTEx, drawn from 953 donors, provides the most statistically robust evidence currently available for this variant
  • No lifestyle or drug-response findings for this variant appear in the provided research materials

What the research says A family-based genome-wide association study (GWAS, a scan of hundreds of thousands of DNA variants across the genome) of attention-deficit/hyperactivity disorder (ADHD) tested 835,136 single-nucleotide polymorphisms (SNPs, single-letter DNA changes) across 735 affected-offspring trios from three U.S. sites; the smallest p-value across all tested variants was 6.7E-07, which did not reach the genome-wide significance threshold of 5.0E-08, and the study's most notable finding was in a different gene, SLC9A9. GTEx v11 expression quantitative trait locus (eQTL, a variant that influences how much of a gene is produced in a cell) data from 953 donors identifies rs11074889 as influencing EMP2 expression in multiple tissues, with the strongest signal in pancreatic tissue (slope +0.40, p=2.4E-9) GTEx Portal. The locus also shows opposing effects on two neighboring genomic elements, ENSG00000279662 and LINC01290, in skin and lung tissue GTEx Portal.

Reported associations

  • ADHD (attention-deficit/hyperactivity disorder): This locus was examined in a 735-trio family-based GWAS of DSM-IV-TR ADHD across three U.S. sites; no genome-wide significant association was reported, and the study's smallest p-value across all 835,136 SNPs tested was 6.7E-07
  • EMP2 expression in pancreas: The alternate allele is linked to increased EMP2 output (slope +0.40, p=2.4E-9, 953 donors) GTEx Portal
  • EMP2 expression in tibial artery: The alternate allele is linked to increased output in this arterial tissue (slope +0.23, p=3.8E-10) GTEx Portal
  • EMP2 expression in tibial nerve: The alternate allele is linked to increased output in nerve tissue (slope +0.17, p=7.1E-6) GTEx Portal
  • EMP2 expression in sun-exposed skin: The alternate allele is linked to increased output in lower-leg skin (slope +0.13, p=1.3E-6) GTEx Portal
  • EMP2 expression in cultured fibroblasts: The alternate allele is linked to increased output in fibroblast (connective-tissue) cell cultures (slope +0.12, p=6.5E-9) GTEx Portal
  • ENSG00000279662 expression in sun-exposed skin: The alternate allele is linked to reduced output of this neighboring gene (slope -0.19, p=1.1E-9) GTEx Portal
  • LINC01290 expression in unexposed suprapubic skin: The alternate allele is linked to reduced output of this long non-coding RNA gene (slope -0.24, p=3.0E-5) GTEx Portal
  • LINC01290 expression in lung: The alternate allele is linked to reduced output of the same long non-coding RNA in lung tissue (slope -0.22, p=3.7E-5) GTEx Portal

Evidence quality The GTEx eQTL associations for this locus are drawn from 953 donors with FDR<0.05 correction applied, and several tissue signals reach p-values well below 1E-8 (tibial artery p=3.8E-10, pancreas p=2.4E-9, ENSG00000279662 in skin p=1.1E-9), lending strong statistical support to the expression findings GTEx Portal. The ADHD GWAS context comes from a single study in which no variant across the entire genome reached significance; any ADHD relevance for this locus must therefore be treated as hypothesis-generating and preliminary, not replicated. No independent replication of an ADHD association at this locus is documented in the provided materials, and the study's own highlighted finding was a different SNP in a different gene entirely.

Tissue-specific expression effects

  • EMP2: The alternate allele is associated with increased expression in pancreas (strongest signal, slope +0.40), tibial artery (slope +0.23), tibial nerve (slope +0.17), sun-exposed lower-leg skin (slope +0.13), and cultured fibroblasts (slope +0.12) GTEx Portal
  • ENSG00000279662: The alternate allele is associated with reduced expression in sun-exposed lower-leg skin (slope -0.19) GTEx Portal
  • LINC01290: The alternate allele is associated with reduced expression of this long non-coding RNA in unexposed suprapubic skin (slope -0.24) and lung tissue (slope -0.22) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What does the EMP2 gene do?

EMP2 (Epithelial Membrane Protein 2) is a gene expressed across several tissue types. Based on GTEx reference data, the rs11074889 variant influences how much EMP2 is produced, with the largest effect measured in pancreatic tissue.

Is rs11074889 linked to ADHD?

This variant was included in a family-based genome-wide association study of ADHD involving 735 family trios, but no genome-wide significant association was reported at this locus. The study's most notable finding was in a different gene, SLC9A9, at a different location in the genome.

Which tissues are affected by rs11074889?

According to GTEx eQTL data from 953 donors, rs11074889 affects EMP2 gene expression in the pancreas, tibial artery, tibial nerve, sun-exposed lower-leg skin, and cultured fibroblasts. It also reduces expression of ENSG00000279662 in sun-exposed skin and LINC01290 in unexposed skin and lung.

What is an eQTL and why does it matter here?

An eQTL (expression quantitative trait locus) is a genetic variant that influences how much of a gene is produced in a cell. rs11074889 is an eQTL for EMP2 and two nearby genomic elements, meaning genotype correlates with measurably different levels of these genes across tissue types.

What is LINC01290?

LINC01290 is a long non-coding RNA gene located near the EMP2 locus. rs11074889 is associated with reduced LINC01290 expression in unexposed skin and lung tissue, though the functional significance of this change is not established in the provided research.