rs11224563 (PGR): Height and Gene Expression

Key takeaways

• Identified in a genome-wide study of 5.4 million people as one of 12,111 variants significantly linked to adult height
• The ALT allele raises PGR gene expression in tibial artery, adrenal gland, cultured fibroblasts, tibial nerve, and aorta
• The same allele also increases PGR-AS1 expression in tibial artery tissue
• Associated with reduced MTMR12P1 expression in tibial nerve tissue
• Height associations were broadly consistent across five major ancestry groups in this study

What the research says rs11224563, located near the PGR gene, is among 12,111 independent SNPs (single-nucleotide polymorphisms - single-letter DNA differences at fixed genome positions) found significantly associated with adult height in a genome-wide association study (GWAS - a large-scale statistical scan linking DNA variants to traits) of 5.4 million participants spanning five ancestry groups PMID 36173670. Together, these variants account for nearly all the common-variant heritability of height (the share of height variation between people attributable to common genetic differences), explaining roughly 40% of height variance in European-ancestry participants and about 10-20% in other groups PMID 36173670. The ALT allele of rs11224563 also shows eQTL effects (statistical links between the variant and tissue-specific gene expression levels) on PGR, most strongly in cultured fibroblasts and adrenal gland, based on GTEx v11 data from 953 donors GTEx Portal.

Reported associations

• Adult height: One of 12,111 SNPs reaching genome-wide significance in a GWAS of 5.4 million individuals across five ancestry groups; the full set explains roughly 40-45% of height variance in European-ancestry participants PMID 36173670
• PGR expression: The ALT allele is associated with increased expression in cultured fibroblasts (slope +0.41), adrenal gland (+0.39), tibial artery (+0.29), tibial nerve (+0.17), and aorta (+0.17) GTEx Portal
• PGR-AS1 expression: The ALT allele is associated with increased expression of this antisense RNA transcript at the same locus in tibial artery tissue (slope +0.24) GTEx Portal
• ENSG00000293058 expression: The ALT allele is associated with increased expression in tibial artery tissue (slope +0.31) GTEx Portal
• MTMR12P1 expression: The ALT allele is associated with reduced expression in tibial nerve tissue (slope -0.26) GTEx Portal

Evidence quality The height association comes from the largest height GWAS described in the provided research, covering 5.4 million participants across five major ancestry groups, with 12,111 SNPs passing genome-wide significance thresholds and associated regions spanning roughly 21% of the genome PMID 36173670. No variant-specific p-value or effect size for rs11224563 itself is reported in the available study text; the variant is catalogued as one of the 12,111 height-associated SNPs. The expression data come from GTEx v11 (953 donors, FDR - false discovery rate - below 0.05), a well-established reference resource GTEx Portal. No independent replication study specific to rs11224563 is present in the provided data, and eQTL associations represent mechanistic signals rather than clinical outcomes.

Tissue-specific expression effects

• PGR: The ALT allele is associated with increased expression in cultured fibroblasts, adrenal gland, tibial artery, tibial nerve, and aorta GTEx Portal
• PGR-AS1: The ALT allele is associated with increased expression in tibial artery tissue GTEx Portal
• ENSG00000293058: The ALT allele is associated with increased expression in tibial artery tissue GTEx Portal
• MTMR12P1: The ALT allele is associated with reduced expression in tibial nerve tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.