Expressive

rs11584700 (LRRN2): Educational Attainment Variant

Key takeaways

  • One of three gene variants that reached genome-wide significance for educational attainment in a study of 126,000+ individuals.
  • Each copy of the effect allele is linked to roughly one additional month of schooling, a very small but statistically robust effect.
  • The association replicated in an independent cohort of 25,490 people and held up across geographic regions and both sexes.
  • Bioinformatics analyses link this locus to the anterior caudate nucleus, a brain region involved in learning and goal-directed behavior.
  • Tissue expression data show this variant alters LRRN2 activity in the liver, thyroid, and esophageal tissues.

Key takeaways

  • rs11584700 is one of three variants that reached genome-wide significance for educational attainment in a discovery sample of 126,000+ individuals.
  • Each copy of the effect allele is linked to roughly one additional month of schooling, a very small but statistically robust effect accounting for approximately 0.02% of variance.
  • The association replicated in an independent cohort of 25,490 individuals and was consistent across geographic regions and both sexes.
  • Bioinformatics analyses of this locus point to the anterior caudate nucleus, a brain region associated with learning and goal-directed behavior.
  • Tissue expression data show this variant influences LRRN2 activity in the liver, thyroid, and esophageal tissues, and PIK3C2B activity in the esophagus and skin.

What the research says A GWAS (genome-wide association study - a method that scans millions of genetic variants across the genome to find those associated with a trait) of 126,559 individuals identified rs11584700, located near the LRRN2 gene (Leucine Rich Repeat Neuronal 2, in the same chromosomal stretch as RNA5SP74), as one of three variants reaching genome-wide significance for educational attainment, with the strongest signal for college completion at p = 2.1 x 10^-9 PMID 23722524. The per-allele effect is small, approximately one additional month of schooling accounting for about 0.02% of variance in educational attainment, and bioinformatics analyses of the locus implicate the anterior caudate nucleus, a brain structure associated with learning and decision-making PMID 23722524.

Reported associations

  • College completion: Genome-wide significant association (p = 2.1 x 10^-9) in a discovery sample of 101,069 individuals, with replication at the Bonferroni-adjusted 5% significance level in an independent cohort of 25,490 participants PMID 23722524
  • Years of schooling (educational attainment): One of three genome-wide significant variants for educational attainment overall; each allele associated with approximately one additional month of schooling (effect size R2 approximately 0.02%) PMID 23722524
  • Cognitive function: A polygenic score (a composite score summing small genetic effects across many variants) derived from all measured SNPs in the same GWAS explains approximately 2% of variance in cognitive function PMID 23722524

Evidence quality The association for this locus comes from a large GWAS meta-analysis across 42 cohorts (discovery n = 101,069; replication n = 25,490) that cleared a stringent genome-wide significance threshold PMID 23722524. The variant replicated at the Bonferroni-adjusted 5% level in an independent sample, with effect estimates of consistent sign and similar magnitude, and showed no notable heterogeneity across geographic regions or sexes PMID 23722524. The per-allele effect is very small (R2 approximately 0.02%, or about one month of schooling per allele), and a polygenic score from all measured SNPs together accounts for only about 2% of variance in educational attainment, reflecting the highly polygenic and environmentally shaped nature of this trait PMID 23722524. No conflicting findings are present in the studies provided.

Tissue-specific expression effects

  • LRRN2: Increased expression in liver, esophagus gastroesophageal junction, esophagus muscularis, and tibial artery; decreased expression in thyroid GTEx Portal
  • PIK3C2B: Increased expression in esophagus mucosa; decreased expression in sun-exposed lower leg skin GTEx Portal
  • PPP1R15B-AS1 (an antisense RNA): Decreased expression in sun-exposed lower leg skin GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11584700?

rs11584700 is a common genetic variant located near the LRRN2 gene, in a chromosomal region also annotated to RNA5SP74. It is one of three variants that reached genome-wide significance for educational attainment in a genetic study of 126,559 individuals.

What does the LRRN2 gene do?

LRRN2 stands for Leucine Rich Repeat Neuronal 2. Tissue expression data show that the rs11584700 variant is associated with altered LRRN2 activity in the liver, esophagus, tibial artery, and thyroid, though the functional consequences of these expression differences are not yet established.

Is rs11584700 linked to intelligence or cognitive function?

A polygenic score combining all genetic variants measured in the same study explains approximately 2% of variance in cognitive function, though rs11584700 alone accounts for only about 0.02% of variance in educational attainment. Educational attainment is shaped by many environmental factors as well.

How strong is the evidence linking rs11584700 to educational attainment?

The evidence comes from a GWAS meta-analysis of 101,069 individuals with independent replication in 25,490 more. The variant cleared a stringent genome-wide significance threshold and replicated at the Bonferroni-adjusted 5% level, with consistent results across geographic regions and sexes. The per-variant effect size is, however, very small.

What brain region is connected to the rs11584700 locus?

Bioinformatics analyses of the locus suggest involvement of the anterior caudate nucleus, a brain region associated with learning, decision-making, and goal-directed behavior.