rs118075465 (LINC03101): SLE Risk in East Asians
Key takeaways
- rs118075465 is among 113 genetic regions linked to lupus risk, identified in a study of more than 208,000 East Asian participants.
- The variant sits near LINC03101 and CTDP1-DT, two genes that produce regulatory RNA molecules rather than proteins.
- Carriers of the ALT allele show reduced activity of the CTDP1-DT gene specifically in thyroid tissue.
- The lupus association met genome-wide significance but comes from a single large study, so independent replication is still needed.
- No drug interactions or lifestyle factors have been reported for this variant.
Key takeaways
- rs118075465 is located near two long non-coding RNA genes, LINC03101 and CTDP1-DT, and was identified as a genetic risk variant for systemic lupus erythematosus (SLE) in East Asian populations.
- The association was discovered in a meta-analysis of more than 208,000 East Asian participants, one of the largest SLE genetics studies in that population to date.
- The variant is among the SLE-associated loci reaching genome-wide significance in the study, which identified 113 susceptibility regions including 46 that were novel.
- In thyroid tissue, the alternative (ALT) allele at this position is associated with reduced expression of the CTDP1-DT gene GTEx Portal.
- Evidence comes from a single large study; independent replication in additional cohorts would strengthen confidence.
What the research says A genome-wide meta-analysis of 13,377 SLE cases and 194,993 controls drawn from East Asian populations identified 113 genetic susceptibility regions for SLE, including 46 novel loci meeting genome-wide significance (p < 5 x 10^-8). rs118075465, in the LINC03101 - CTDP1-DT region (a segment of the genome encoding long non-coding RNAs, which are RNA molecules that do not produce proteins but may regulate other genes), was identified among these SLE-associated loci. Separately, expression data from the GTEx project show that the ALT allele at rs118075465 is associated with reduced expression of CTDP1-DT specifically in thyroid tissue GTEx Portal.
Reported associations
- Systemic lupus erythematosus (SLE): Associated with SLE risk at genome-wide significance in an East Asian meta-analysis of 13,377 cases and 194,993 controls (total n approximately 208,370); the specific odds ratio for this variant is not reported in the available study text.
- CTDP1-DT expression in thyroid tissue: The ALT allele is associated with reduced CTDP1-DT gene expression in thyroid tissue (effect slope -0.34 in log2-normalized units, GTEx v11, n=953 donors, p=1.3 x 10^-4) GTEx Portal.
Evidence quality The SLE association is based on a large-scale East Asian genome-wide meta-analysis (total n approximately 208,370, comprising 13,377 cases and 194,993 controls) meeting the standard genome-wide significance threshold (p < 5 x 10^-8). The study applied Bayesian statistical fine-mapping to prioritize causal variants, narrowing 28 association signals to credible sets of 10 or fewer variants and identifying 110 putative causal variants with posterior probability >= 0.1 across 57 SLE loci, including 10 highest-confidence causal variants with posterior probability >= 0.8. The available study text does not report the specific effect size or posterior probability for rs118075465 individually, so it is not possible to determine whether it falls within the highest-confidence tier. No independent replication cohort result is described for this variant in the available text, which limits confidence. The GTEx eQTL (expression quantitative trait locus, meaning a genetic variant associated with variation in a gene's activity level) signal in thyroid tissue (p=1.3 x 10^-4) represents a possible biological mechanism but does not establish a causal link to SLE or thyroid disease.
Tissue-specific expression effects
- CTDP1-DT: The ALT allele is associated with reduced expression in thyroid tissue; this signal was detected in GTEx v11 (953 donors, cis-window analysis, FDR < 0.05) GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs118075465?
rs118075465 is a single-letter variation in the human genome located near LINC03101 and CTDP1-DT, two long non-coding RNA genes. It has been associated with risk for systemic lupus erythematosus in a large study of East Asian populations.
What is systemic lupus erythematosus (SLE)?
Systemic lupus erythematosus is an autoimmune disorder in which the immune system produces autoantibodies that can damage multiple organs throughout the body.
What does CTDP1-DT do?
CTDP1-DT is a long non-coding RNA gene, meaning it produces an RNA molecule that does not code for a protein. Its precise biological role is not yet fully established, but expression data show that nearby genetic variants can influence its activity in thyroid tissue.
Is rs118075465 linked to thyroid conditions?
No thyroid disease association has been reported for this variant in the available research. Expression data from GTEx do show that the ALT allele is associated with lower CTDP1-DT activity in thyroid tissue, which may inform future mechanistic research but does not constitute a disease link.
How confident are researchers in the lupus association for rs118075465?
The association reached genome-wide significance in a meta-analysis of more than 208,000 East Asian participants, which is a high bar. However, the specific effect size for this variant is not publicly reported in the available study text and independent replication has not yet been described, so the evidence is considered preliminary.