rs11723349 (CLNK): Cognitive Function Variant
Key takeaways
- Found among 148 loci linked to general cognitive function in a 300,000-person genome-wide study
- The alternative allele increases CLNK expression in cerebellar brain regions
- Also associated with increased HS3ST1 expression in brain and peripheral nerve tissue
- LINC02498, a non-coding RNA at this locus, shows increased expression in immune cells
- No lifestyle or drug-response links have been documented for this variant
Key takeaways
- Found among 148 loci linked to general cognitive function in a 300,000-person genome-wide study
- The alternative allele increases CLNK expression in cerebellar brain regions
- Also associated with increased HS3ST1 expression in brain and peripheral nerve tissue
- LINC02498, a non-coding RNA at this locus, shows increased expression in immune cells
- No lifestyle or drug-response links have been documented for this variant
What the research says A genome-wide association study (GWAS - a method that scans the genomes of large populations to identify variants statistically linked to a trait) combining data from the CHARGE and COGENT consortia and UK Biobank (n=300,486, age 16-102) identified 148 independent loci at genome-wide significance (p<5x10^-8) for general cognitive function; the CLNK - LINC02498 (long intergenic non-coding RNA 02498, meaning a stretch of DNA transcribed into RNA that does not encode a protein) region was among them. Polygenic scores (a composite measure summing the small effects of many genetic variants across the genome) derived from those 148 loci predicted up to 4.3% of variance in cognitive function in independent samples. The 148 loci collectively overlapped with pathways linked to neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure, though these pathway enrichments are reported for the full locus set rather than for this locus individually.
Reported associations
- General cognitive function: This locus was among 148 genome-wide significant findings (p<5x10^-8) in a GWAS of 300,486 individuals spanning age 16-102; no per-variant effect size specifically for rs11723349 is reported in the available study text.
Evidence quality The association with cognitive function comes from a single large-scale GWAS (n=300,486) published in 2018 in Nature Communications, representing a well-powered discovery cohort. The study met genome-wide significance for this locus, but specific per-variant statistics for rs11723349 are not detailed in the available text. Polygenic scores across all 148 loci together explained up to 4.3% of cognitive function variance in independent samples; this figure reflects the combined 148-locus set and cannot be attributed to this locus alone. No independent replication specific to rs11723349 is described in the provided materials, which limits confidence in the individual-variant association. Separate GTEx eQTL data (GTEx v11, 953 donors) provides strong independent evidence of a regulatory role in cerebellar tissue, with CLNK expression in Brain Cerebellar Hemisphere showing slope +0.71 (p=8.7x10^-14) and in Brain Cerebellum slope +0.63 (p=3.9x10^-11); HS3ST1 shows smaller but statistically supported increases in cerebellum (slope +0.30), cerebellar hemisphere (slope +0.25), and tibial nerve (slope +0.19) GTEx Portal.
Tissue-specific expression effects
- CLNK: Increased expression in Brain Cerebellar Hemisphere and Brain Cerebellum GTEx Portal
- HS3ST1: Increased expression in Brain Cerebellum, Brain Cerebellar Hemisphere, and Nerve Tibial GTEx Portal
- LINC02498: Increased expression in EBV-transformed lymphocytes (immune cells maintained in laboratory culture) GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs11723349?
rs11723349 is a common genetic variant in the CLNK-LINC02498 genomic region. It was identified in a large population study as one of 148 loci statistically associated with general cognitive function across more than 300,000 individuals.
What does the CLNK gene do?
The available research does not describe the specific biological role of CLNK in cognition. The association was found through a genome-wide statistical scan rather than a study of CLNK molecular function.
Is rs11723349 linked to intelligence or memory?
It is one of 148 genetic loci that collectively reached statistical significance in a large study of general cognitive function. All 148 loci together account for up to 4.3% of cognitive function variance, but no individual effect size for this specific variant is documented in the available research.
What is an eQTL and why does it matter for this variant?
An eQTL (expression quantitative trait locus) is a genetic variant that influences how actively a nearby gene is expressed in a specific tissue. For rs11723349, data from the GTEx project show it raises CLNK expression in two cerebellar brain regions, which may suggest a regulatory mechanism - though eQTL effects describe gene regulation, not a direct health outcome.
How reliable is the cognitive function finding for rs11723349?
The association comes from a single large discovery study of over 300,000 people that met genome-wide significance thresholds. No independent replication specific to this variant is documented in the available research, so the finding should be considered preliminary.