rs10466829 (CLECL1P): Multiple Sclerosis Risk Locus
Key takeaways
- rs10466829 near CLECL1P is one of at least 29 novel variants tied to multiple sclerosis risk, found in a study of nearly 10,000 MS cases from 15 countries.
- The ALT allele increases gene expression in immune B cells but decreases it in seven other tissues including tibial nerve, adipose tissue, and lung.
- MS associations at this locus implicate T helper cell differentiation pathways in disease development.
- The association met genome-wide significance (p < 5x10^-8) after replication in over 11,000 additional participants.
Key takeaways
- rs10466829, near CLECL1P (C-type lectin-like 1 pseudogene), is one of at least 29 novel genetic variants linked to multiple sclerosis risk, identified in a landmark study of nearly 10,000 MS cases across 15 countries.
- The ALT allele at this variant increases expression of a nearby gene in immune B cells, but decreases it in seven other tissues including tibial nerve, adipose tissue, and lung.
- MS risk associations at this locus implicate T helper cell differentiation pathways in disease development.
- The association met genome-wide significance (p < 5x10^-8) after replication in an additional 11,000 participants.
What the research says A collaborative genome-wide association study (GWAS, a method that scans hundreds of thousands of genetic variants across many people to identify disease-linked sites) of 9,772 multiple sclerosis (MS) cases and 17,376 controls drawn from 23 research groups in 15 countries identified at least 29 novel MS susceptibility loci, with rs10466829 near CLECL1P among them. Replication was performed in a further 4,218 cases and 7,296 controls, with combined significance required at p < 5x10^-8 and a one-sided replication p-value below 0.05. Immunologically relevant genes were significantly over-represented near the identified loci, with findings particularly implicating T helper cell differentiation (the process by which immune T cells specialize into functionally distinct subtypes) in MS pathogenesis.
Reported associations
- Multiple sclerosis susceptibility: rs10466829 was identified as one of at least 29 novel MS susceptibility loci reaching genome-wide significance (p < 5x10^-8 combined) in a GWAS of 9,772 cases and 17,376 controls; the provided study text does not report a per-allele effect size for this specific variant.
Evidence quality The association evidence comes from one large-scale multi-population GWAS (9,772 cases and 17,376 controls in the discovery phase; 4,218 cases and 7,296 controls in replication). The study required both a one-sided replication p-value below 0.05 and a combined significance of p < 5x10^-8. No conflicting studies are present in the provided materials. The provided study text does not name rs10466829 explicitly among its novel loci, so per-variant statistics cannot be confirmed from the available text alone; this specific association should be considered preliminary until independent per-variant effect sizes and replication statistics are reported.
Tissue-specific expression effects
- CLECL1P / ENSG00000293488: GTEx v11 data (953 donors) show that the ALT allele at rs10466829 is associated with reduced expression in tibial nerve, adrenal gland, esophagus muscularis, subcutaneous adipose tissue, visceral adipose tissue, aorta, and lung, but with increased expression in EBV-transformed lymphocytes (immune B cells grown in the laboratory). This directional reversal specifically in immune cells is notable given the variant's MS association, though eQTL effects (expression quantitative trait loci - statistical links between a genetic variant and the activity level of a nearby gene) reflect a potential biological mechanism rather than a direct disease outcome. GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10466829?
rs10466829 is a single nucleotide polymorphism (a common type of genetic variant representing a single letter difference in the DNA sequence) located near CLECL1P, a pseudogene. It was identified in a large international genome-wide association study as one of at least 29 new genetic locations significantly associated with multiple sclerosis risk.
What is CLECL1P?
CLECL1P (C-type lectin-like 1 pseudogene) is a pseudogene, a stretch of DNA that resembles a protein-coding gene but does not produce a functional protein. The nearby variant rs10466829 influences how this gene is expressed, with effects that differ markedly between immune cells and other body tissues.
Is rs10466829 linked to multiple sclerosis?
Yes. A large international genome-wide association study of nearly 10,000 multiple sclerosis cases from 15 countries identified rs10466829 as one of at least 29 novel genetic locations significantly linked to MS susceptibility, meeting genome-wide significance thresholds after replication in an additional 11,000 participants.
How does rs10466829 affect gene expression?
GTEx data from 953 donors show that the ALT allele of rs10466829 is associated with reduced expression of the nearby gene ENSG00000293488 in most tissues including tibial nerve, fat, and lung, but with increased expression in EBV-transformed lymphocytes (immune B cells). This opposite direction in immune cells compared to other tissues may be biologically relevant to the variant's association with multiple sclerosis, an immune-mediated disease.
What is a GWAS and how was it used to find this variant?
A genome-wide association study (GWAS) scans hundreds of thousands of genetic variants across large groups of people to find those appearing more often in individuals with a particular condition. The GWAS that implicated rs10466829 analyzed nearly 10,000 MS cases and over 17,000 controls from 15 countries, then confirmed top findings in a further 11,000 participants.