rs12003641 (ECPAS/ZNF483): Height and PTGR1 Expression

Key takeaways

• rs12003641 sits near ECPAS and ZNF483 and is one of 12,111 SNPs identified as height-associated in a study of over 5.4 million individuals.
• The ALT allele consistently reduces PTGR1 gene expression across at least eight tissues including heart, aorta, ovary, and brain.
• The 12,111 height SNPs as a set explain roughly 40% of height variance in European-ancestry populations, dropping to 10-20% in other ancestries.
• The ovary shows the largest PTGR1 expression reduction, with consistent but smaller effects in cardiovascular and metabolic tissues.
• No per-SNP effect size for rs12003641 on height is available in current study materials.

What the research says A genome-wide association study of 5,380,080 individuals from 281 studies identified 12,111 independent SNPs significantly associated with adult height, organized within 7,209 non-overlapping genomic segments with a mean size of roughly 90 kb covering about 21% of the genome; this SNP set collectively explains approximately 40% (up to 45%) of height variance in European-ancestry populations and roughly 10-20% in other ancestry groups. GTEx expression-QTL data from 953 donors shows that the ALT allele at rs12003641 is associated with reduced PTGR1 expression (FDR less than 0.05) across eight tissues spanning cardiovascular, reproductive, nervous, and metabolic tissue types GTEx Portal. No individual effect size or p-value for rs12003641 specifically on height is available in the provided study text.

Reported associations

• Adult height: rs12003641 is one of 12,111 SNPs identified as significantly associated with height in a sample of 5.4 million individuals; the full SNP set explains roughly 40% of height variance in European populations and approximately 10-20% in other ancestry groups.
• PTGR1 expression (eQTL): The ALT allele is associated with reduced PTGR1 expression in ovary (largest effect), brain amygdala, heart atrial appendage, aorta, tibial artery, esophagus muscularis, subcutaneous adipose tissue, and sun-exposed lower-leg skin GTEx Portal.

Evidence quality The height association is supported by the largest height GWAS conducted to date, covering more than 5.4 million participants across five broad ancestry groups including European, East Asian, Hispanic, African, and South Asian populations; the study identified loci reaching genome-wide significance and the combined SNP set was shown to approach predicted limits for common-variant prediction accuracy in European populations. However, no per-SNP statistics for rs12003641 individually are reported in the available study text, so its specific independent contribution to height variance cannot be quantified from current evidence. The eQTL evidence from GTEx is based on 953 donors at FDR less than 0.05, replicated consistently across eight distinct tissues, suggesting a robust functional signal at this locus GTEx Portal. No conflicting findings are reported across the provided evidence sources.

Tissue-specific expression effects

• PTGR1: The ALT allele is associated with reduced expression in ovary, brain amygdala, heart atrial appendage, aorta, tibial artery, esophagus muscularis, subcutaneous adipose tissue, and sun-exposed lower-leg skin; the largest reductions are seen in ovary tissue and brain amygdala, with smaller but statistically significant reductions across cardiovascular and metabolic tissues GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.