rs12192568 (GPR89P/RSL24D1P1): Korean GWAS novel locus
Key takeaways
- Identified as a novel genetic locus in a 153,950-person Korean genome-wide association study of 36 quantitative traits
- The alternative allele reduces expression of ZSCAN31 and SCAND3 in the pancreas
- The alternative allele reduces ZNF603P expression in the lung and thyroid
- ZNF391 expression is increased in coronary artery tissue in carriers of the alternative allele
- ZSCAN23 expression is reduced in the substantia nigra (a brain region) and tibial artery
Key takeaways
- Identified as a novel genetic locus in a 153,950-person Korean genome-wide association study (GWAS) of 36 quantitative traits
- The alternative allele reduces expression of ZSCAN31 and SCAND3 in the pancreas
- The alternative allele reduces ZNF603P expression in the lung and thyroid
- ZNF391 expression is increased in coronary artery tissue in carriers of the alternative allele
- ZSCAN23 expression is reduced in the substantia nigra (a brain region) and tibial artery
What the research says This variant lies in the GPR89P - RSL24D1P1 region, named for two flanking pseudogenes (genomic sequences resembling genes but no longer producing functional protein), and was among 301 previously unreported genetic loci identified in a GWAS of 153,950 Korean individuals across 36 quantitative traits spanning anthropometric, metabolic, hematological, and cardiovascular phenotypes. GTEx v11 data from 953 donors classifies this locus as an expression quantitative trait locus (eQTL) - meaning the variant correlates with altered expression of nearby genes in the same chromosomal neighborhood - with effects documented across six genes in five tissue types GTEx Portal. All six affected genes belong to the zinc finger protein family, and the alternative allele predominantly reduces their expression in the pancreas, lung, thyroid, and arterial and brain tissues, with the exception of ZNF391 in coronary artery tissue where expression is increased GTEx Portal.
Reported associations
- Novel GWAS locus (Korean population): Among 301 loci not previously reported in predominantly European GWAS catalogs, identified in the Korean Cancer Prevention Study-II (KCPS2) Biobank of 153,950 individuals across 36 quantitative traits
- ZSCAN31 expression in pancreas: Alternative allele associated with reduced expression in pancreatic tissue (beta -0.50, p = 5.8e-6) GTEx Portal
- ZNF603P expression in lung: Alternative allele associated with reduced expression in lung tissue (beta -0.39, p = 2.1e-6) GTEx Portal
- ZNF603P expression in thyroid: Alternative allele associated with reduced expression in thyroid tissue (beta -0.38, p = 1.9e-7) GTEx Portal
- ZNF391 expression in coronary artery: Alternative allele associated with increased expression in coronary artery tissue (beta +0.50, p = 1.2e-5) GTEx Portal
- ZSCAN23 expression in substantia nigra: Alternative allele associated with reduced expression in the substantia nigra, a brain region (beta -0.52, p = 1.4e-4) GTEx Portal
- ZSCAN23 expression in tibial artery: Alternative allele associated with reduced expression in tibial artery tissue (beta -0.32, p = 1.3e-6) GTEx Portal
- SCAND3 expression in pancreas: Alternative allele associated with reduced expression in pancreatic tissue (beta -0.39, p = 5.6e-6) GTEx Portal
- ENSG00000294464 expression in pancreas: Alternative allele associated with reduced expression of an uncharacterized gene in pancreatic tissue (beta -0.46, p = 3.4e-5) GTEx Portal
Evidence quality The GWAS evidence is from a single large Korean cohort (KCPS2, n = 153,950) using a linear mixed model with appropriate population stratification controls (median genomic inflation factor lambda 1.23, S-LDSC intercept 1.04); no PMID is available for this publication. Independent replication of the variant's GWAS associations has not been reported in the provided materials. The eQTL evidence is from GTEx v11 (953 donors, FDR < 0.05), a well-powered population-level reference dataset; beta coefficients represent the estimated change in log2-normalized gene expression per copy of the alternative allele, so a beta of -0.52 (ZSCAN23 in substantia nigra) indicates a moderate expression reduction. eQTL associations are statistical correlations and do not on their own establish causal mechanisms or disease relevance. The convergence of three independent pancreatic eQTL signals at this locus (ZSCAN31 beta -0.50, SCAND3 beta -0.39, ENSG00000294464 beta -0.46) is notable, but its biological significance is not characterized in the available evidence.
Tissue-specific expression effects
- ZSCAN31: Reduced expression in pancreatic tissue GTEx Portal
- ZNF603P: Reduced expression in lung and thyroid tissue GTEx Portal
- ZNF391: Increased expression in coronary artery tissue GTEx Portal
- ENSG00000294464: Reduced expression in pancreatic tissue GTEx Portal
- ZSCAN23: Reduced expression in the substantia nigra and in tibial artery tissue GTEx Portal
- SCAND3: Reduced expression in pancreatic tissue GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs12192568?
rs12192568 is a genetic variant located near two pseudogenes, GPR89P and RSL24D1P1. It was identified as a novel locus in a large Korean genome-wide association study and shows tissue-specific effects on the expression of nearby zinc finger genes across the pancreas, lung, thyroid, coronary artery, and brain.
What are GPR89P and RSL24D1P1?
GPR89P is a pseudogene - a non-functional genomic remnant resembling a gene that once encoded a G protein-coupled receptor. RSL24D1P1 is another pseudogene in the same chromosomal region. Both serve as positional landmarks for this variant but do not produce functional proteins themselves.
What does the rs12192568 variant do to gene expression?
GTEx v11 data from 953 donors shows the alternative allele reduces expression of ZSCAN31 and SCAND3 in the pancreas, reduces ZNF603P in the lung and thyroid, and reduces ZSCAN23 in the brain substantia nigra and tibial artery. In contrast, it increases ZNF391 expression in coronary artery tissue.
Is rs12192568 linked to any disease?
The available evidence does not establish a direct link to any specific disease. The variant was flagged in a broad Korean GWAS of 36 quantitative traits and its tissue-specific gene expression effects are documented, but the functional consequences of those expression changes are not characterized in the current evidence.
What are zinc finger genes like ZSCAN31 and ZNF391?
Zinc finger proteins are a large family of proteins named for a structural motif that coordinates a zinc ion. ZSCAN31, ZSCAN23, ZNF391, ZNF603P, and SCAND3 all belong to this family. Their specific roles in the tissues where rs12192568 affects their expression are not fully characterized in the current evidence.