Expressive

rs10985070 (PHF19): Refractive Error and RA Variant

Key takeaways

  • rs10985070 is located near PHF19, a gene involved in controlling which genes are active in a cell by modifying how DNA is packaged
  • GTEx v11 data from 953 donors show this variant reduces expression of the CUTALP gene across eight tissue types, from thyroid and lung to whole blood and skeletal muscle
  • The studies associated with this entry include large genome-wide analyses of refractive error (over 1.76 million participants) and rheumatoid arthritis (over 100,000 subjects), mapping the broader genomic landscape in which this locus sits
  • All associations described here come from population-level statistical research and do not predict individual health outcomes

Key takeaways

  • rs10985070 is located near PHF19 (plant homeodomain finger protein 19), a gene involved in controlling which genes are active in a cell by modifying how DNA is packaged
  • GTEx v11 data from 953 donors show this variant reduces expression of the CUTALP gene across eight tissue types, from thyroid and lung to whole blood and skeletal muscle
  • The studies provided for this entry include large genome-wide analyses of refractive error (over 1.76 million participants) and rheumatoid arthritis (over 100,000 subjects), mapping the broader genomic landscape in which this locus sits
  • All associations described here come from population-level statistical research and do not predict individual health outcomes

What the research says

GTEx v11 data (953 donors, false discovery rate < 0.05) show that the alternate allele at rs10985070 is a cis-eQTL (a genetic variant that influences the expression of a nearby gene) for CUTALP in at least eight tissues, consistently reducing expression in each GTEx Portal. A cross-ancestry genome-wide association meta-analysis of refractive error enrolling 1,495,159 participants of European ancestry, 121,172 of East Asian ancestry, and 144,737 of African ancestry identified 932 associated variants, including 241 novel associations, and constructed a polygenic predictor explaining 21.4% of refractive error variation with an area under the ROC curve of 0.806 for high myopia prediction. Separate genome-wide association studies of rheumatoid arthritis (RA) - covering a Northwestern European cohort of 31,313 cases and approximately 1 million controls, plus trans-ethnic analyses exceeding 100,000 subjects - mapped over 100 non-HLA RA risk loci and identified candidate causal genes concentrated in the JAK/STAT and interferon-alpha/beta signaling pathways.

Reported associations

  • CUTALP gene expression (eQTL): The alternate allele at this locus directly reduces expression of the CUTALP gene in at least eight tissue types, with the strongest reduction observed in thyroid; all measured tissues show decreased expression and none show increased expression GTEx Portal
  • Refractive error (surrounding genomic region): A multi-ancestry GWAS of over 1.76 million participants identified 932 refractive error variants, including 241 novel associations; a resulting polygenic predictor explains 21.4% of refractive error variation and achieves an area under the ROC curve of 0.806 for high myopia prediction; the study text does not name this specific variant by identifier
  • Rheumatoid arthritis (surrounding genomic region, seropositive subset): Multiple large RA GWAS - a Northwestern European study (31,313 cases, approximately 1 million controls), a trans-ethnic meta-analysis (>100,000 subjects), and an African-American analysis (916 cases, 1,392 controls) - collectively mapped over 100 non-HLA risk loci, with the strongest signals in the seropositive subset pointing to JAK/STAT and interferon-alpha/beta pathway genes; the study texts do not name this specific variant by identifier

Evidence quality

GTEx eQTL evidence is the most direct for rs10985070, based on 953 donors with tissue-level expression profiling at false discovery rate < 0.05; consistent directionality across eight distinct tissues strengthens confidence in the CUTALP expression finding. The refractive error GWAS is among the largest conducted for any eye trait, totaling over 1.76 million participants across three ancestry groups, with statistical fine-mapping pinpointing 16 high-confidence putative causal variants and a polygenic predictor reaching an area under the ROC curve of 0.806. The RA GWAS literature spans a genome-wide-significant (p < 5 x 10^-8) Northwestern European study of 31,313 cases and approximately 1 million controls, a trans-ethnic meta-analysis exceeding 100,000 subjects, and an African-American-specific analysis (916 cases, 1,392 controls) that identified two ancestry-specific loci (GPC5 and RBFOX1) and seven novel high-confidence candidate pathogenic variants. None of the provided study excerpts name rs10985070 or PHF19 by identifier; variant-level statistics for this specific SNP within the GWAS papers are not available in the provided source text and would need to be verified in the full supplementary data of each study.

Tissue-specific expression effects

  • CUTALP: Reduced expression in thyroid (strongest signal among reported tissues), tibial artery, lung, sun-exposed lower leg skin, tibial nerve, subcutaneous adipose tissue, skeletal muscle, and whole blood; all eight tissues show the same direction of effect (decreased expression) and none show increased expression GTEx Portal

Lifestyle considerations

No lifestyle considerations on file for this variant.

Frequently asked questions

What is PHF19 and what does it do?

PHF19 (plant homeodomain finger protein 19) is a gene involved in chromatin regulation, meaning it helps control which genes in a cell are switched on or off by modifying how DNA is physically packaged. It is part of a protein complex that influences gene expression across many biological processes.

What does rs10985070 actually change in the body?

Based on GTEx v11 data from 953 donors, the alternate allele at rs10985070 is associated with reduced expression of a gene called CUTALP across at least eight tissue types including thyroid, lung, blood, and skeletal muscle. This is an expression-level effect; the available sources do not directly link it to a specific clinical outcome.

Is rs10985070 associated with myopia or refractive error?

A large multi-ancestry genome-wide study of over 1.76 million participants identified 932 refractive error variants and is among the studies provided for this locus. The available study text does not name rs10985070 by identifier, so a directly confirmed association with myopia cannot be stated from the provided source material.

Is rs10985070 linked to rheumatoid arthritis?

Several large genome-wide association studies of rheumatoid arthritis - covering Northern European, East Asian, and African-American populations - are provided as reference literature for this locus. The provided study texts do not name this specific variant by identifier, so a directly confirmed RA association cannot be stated from the available excerpts.

What is an eQTL and why is the CUTALP finding relevant?

An eQTL (expression quantitative trait locus) is a genetic variant that influences how much of a particular gene is produced in a cell. The consistent reduction in CUTALP expression across eight distinct tissues in GTEx data suggests this variant may have a broad effect on gene regulation, though the provided sources do not link reduced CUTALP expression to a specific clinical outcome.