Expressive

rs12144380 (PTPRC): Lupus Risk Variant

Key takeaways

  • rs12144380 near PTPRC is associated with systemic lupus erythematosus based on a multi-ancestry study covering over 718,000 individuals from three population groups.
  • The source study identified 16 novel genetic loci for lupus and highlighted non-classical monocytes and B cells as cell types enriched for putative target genes.
  • GTEx data show the alternate allele is linked to reduced PTPRC expression in tibial nerve tissue, pointing to a regulatory role at this locus.
  • No specific per-allele effect size was available in the study excerpt, so the magnitude of risk change at this locus remains unconfirmed.

Key takeaways

  • rs12144380 sits at a locus containing two genes, ATP6V1G3 and PTPRC, and has been associated with systemic lupus erythematosus (SLE) in a large multi-ancestry genetic study.
  • The study is among the largest SLE analyses to date, combining data from over 718,000 participants across three ancestries: European, East Asian, and Admixed American.
  • GTEx eQTL (expression quantitative trait locus) data show the alternate allele at this position is linked to reduced PTPRC expression in tibial nerve tissue.
  • No specific per-allele odds ratio was available in the study excerpt, so the magnitude of risk change associated with this variant remains unconfirmed.

What the research says A multi-ancestry, multi-trait genome-wide association meta-analysis identified a statistically significant signal at this locus in the context of SLE, drawing on 12 cohorts from European, East Asian, and Admixed American ancestries (21,625 cases and 696,841 controls total) and applying a genome-wide significance threshold of p < 5 x 10^-8; the study identified 16 novel SLE loci in total and conducted downstream transcriptome-wide association studies and cell type enrichment analyses, with non-classical monocytes and B cells among the cell types highlighted as enriched for putative target genes across all identified loci. GTEx v11 data independently show the alternate allele at rs12144380 is associated with reduced PTPRC expression in tibial nerve tissue (p = 1.7 x 10^-4). GTEx Portal

Reported associations

  • Systemic lupus erythematosus (SLE): rs12144380 was identified in a multi-ancestry GWAS meta-analysis of SLE (21,625 cases, 696,841 controls across three ancestries); no specific per-allele odds ratio was available in the text excerpt provided.

Evidence quality The source study encompasses over 718,000 participants and rigorously applies genome-wide significance thresholds (p < 5 x 10^-8). The multi-ancestry design, covering three distinct population groups, improves generalizability relative to single-ancestry studies. However, no PMID was provided for the source publication, and the specific per-allele effect size for rs12144380 is not confirmed from the available text excerpt. Whether this locus is among the 16 newly reported loci or represents a previously known association cannot be determined from the excerpt alone. The GTEx eQTL finding is based on 953 donors under FDR < 0.05 criteria, representing moderate mechanistic evidence. Overall, this locus should be considered preliminary evidence pending independent replication.

Tissue-specific expression effects

  • PTPRC: The alternate allele at rs12144380 is associated with reduced PTPRC expression in tibial nerve tissue (GTEx v11, p = 1.7 x 10^-4, FDR < 0.05), indicating a statistically significant but modest regulatory effect at this tissue site. GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs12144380 associated with?

rs12144380, located at the ATP6V1G3-PTPRC locus, has been associated with systemic lupus erythematosus (SLE), a chronic autoimmune disease, in a large multi-ancestry genome-wide association study covering over 718,000 individuals from European, East Asian, and Admixed American ancestries.

Does rs12144380 affect gene expression?

GTEx v11 data show the alternate allele at rs12144380 is associated with reduced PTPRC expression in tibial nerve tissue (p = 1.7 x 10^-4, FDR < 0.05). Expression effects in other tissues may exist but are not captured in the dataset provided.

How large was the study that identified this variant?

The source study was a multi-ancestry meta-analysis of 12 cohorts covering 21,625 SLE cases and 696,841 controls, totaling over 718,000 individuals from three ancestries.

Is rs12144380 a newly discovered lupus locus?

The source study identified 16 novel SLE loci, but the available text does not confirm whether rs12144380 is one of those newly reported loci or a confirmation of a previously known association.

What genes are at the rs12144380 locus?

The rs12144380 locus is annotated to two genes: ATP6V1G3 and PTPRC. GTEx eQTL data provided covers expression effects for PTPRC specifically, showing reduced expression in tibial nerve tissue for the alternate allele.