rs1026997 (NEGR1): Intelligence-Linked Brain Variant
Key takeaways
- rs1026997, in the NEGR1 gene, was one of 187 genome-wide significant loci for intelligence in a study of ~248,000 participants.
- The variant affects expression of nearby genes RPL31P12 and LINC02796 in brain regions including the cerebellum and cortex.
- This gene also shows increased expression in visceral fat tissue in carriers of the alternate allele.
- Biological pathways implicated in the broader intelligence study include neurogenesis and myelination.
- Intelligence is highly polygenic - each of the 187 associated loci, including rs1026997, contributes only a small individual effect.
Key takeaways
- rs1026997, in the NEGR1 gene, was one of 187 genome-wide significant loci for intelligence discovered in a study of ~248,000 participants.
- The variant affects expression of nearby genes RPL31P12 and LINC02796 in brain regions including the cerebellum and cortex.
- This gene also shows increased expression in visceral fat tissue in carriers of the alternate allele - a finding that sits at some distance from its intelligence association.
- Biological pathways implicated in the broader intelligence study include neurogenesis and myelination (the formation of the insulating myelin sheath around nerve cells).
- Intelligence is highly polygenic, meaning each of the 187 associated loci - including rs1026997 - contributes only a small individual effect to the trait.
What the research says A multi-trait genome-wide association study (GWAS - a population-scale scan that links genetic variants to traits) combined summary statistics from two large datasets on intelligence and educational attainment, exploiting their strong genetic correlation (rg = 0.70) to reach a functional sample of 248,482 participants; rs1026997 in the NEGR1 gene was among 187 independent loci that reached genome-wide significance, with 538 genes implicated in total. The study found evidence that neurogenesis (the generation of new nerve cells), myelination, and genes active at synapses and in nervous system regulation may underlie biological differences in intelligence. Because intelligence is a highly polygenic trait (shaped by many variants, each with a small effect), this variant is expected to account for only a small fraction of total trait variance.
Reported associations
- Intelligence (general cognitive function): rs1026997 was identified among 187 genome-wide significant loci in a multi-trait GWAS combining intelligence and educational attainment summary statistics, with a functional sample size of 248,482 participants and 538 genes implicated across all significant loci.
Evidence quality The association rests on a large discovery-stage GWAS that used multi-trait analysis (MTAG) to combine summary statistics from two datasets, reaching a functional sample of 248,482. Combining intelligence and educational attainment data (rg = 0.70) increases statistical power but relies on the assumption that the traits share sufficient genetic architecture - the authors report validation analyses supporting this. The provided study text does not report a specific p-value or effect size for rs1026997 individually, so variant-level statistical strength cannot be assessed from the available information. The study does not describe explicit replication of this specific variant, so the association should be treated as discovery-level evidence pending independent confirmation.
Tissue-specific expression effects
- RPL31P12: The alternate allele at rs1026997 is associated with increased expression of this gene in the brain cerebellum and cerebellar hemisphere GTEx Portal.
- LINC02796: The alternate allele is associated with reduced expression of this long non-coding RNA (a class of RNA that does not code for protein) in the brain cortex and anterior cingulate cortex (BA24, a region involved in attention and decision-making) GTEx Portal.
- NEGR1: The alternate allele is associated with increased expression of NEGR1 in visceral adipose tissue (fat surrounding internal organs, sampled from the omentum) GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs1026997?
rs1026997 is a common genetic variant located in the NEGR1 gene. It was identified as one of 187 genome-wide significant loci statistically linked to intelligence in a large multi-trait study of approximately 248,000 participants.
What does the NEGR1 gene do?
The intelligence study that flagged rs1026997 found that genes at implicated loci cluster around neurogenesis and nervous system functions. GTEx data separately show that carriers of the alternate allele have increased NEGR1 expression in visceral fat tissue, though the available studies do not assign a specific cognitive function to NEGR1 alone.
Is rs1026997 linked to intelligence?
A multi-trait genome-wide study of approximately 248,000 participants found rs1026997 to be one of 187 genome-wide significant loci for intelligence. Because intelligence is highly polygenic, the individual contribution of this single variant is small.
What tissues does rs1026997 affect gene expression in?
GTEx data show that the alternate allele at rs1026997 is linked to increased expression of RPL31P12 in the brain cerebellum, reduced expression of LINC02796 in the brain cortex and anterior cingulate cortex, and increased expression of NEGR1 in visceral fat tissue.
What does genome-wide significance mean for a variant like this?
Genome-wide significance means the statistical association between rs1026997 and intelligence is robust enough to stand out across millions of tested variants in a large population. It does not imply a large individual effect - intelligence is shaped by hundreds of variants, and this one contributes only a small fraction of the total genetic influence.