rs12110525 (BDH2P1/FAXC): Height and Gene Expression

Key takeaways

• rs12110525 is one of 12,111 SNPs identified as significantly associated with adult height in a genome-wide study of 5.4 million people from diverse ancestries.
• Together, these height-associated variants explain roughly 40% of height variation in European ancestry populations and 10-24% in other ancestries.
• The alternate allele at this locus is linked to reduced expression of the FBXL4 gene in esophageal and thyroid tissue, based on GTEx eQTL data.
• No individual effect size for this specific variant on height is available from the study text.

What the research says rs12110525, near the BDH2P1 and FAXC loci, was identified as one of 12,111 independent SNPs significantly associated with adult height in a genome-wide association study (GWAS, a method that scans the entire genome for trait-linked variants) of approximately 5.4 million individuals spanning European, East Asian, Hispanic, African, and South Asian ancestries PMID 36224396. These height-associated variants collectively fall within 7,209 genomic segments covering about 21% of the genome and account for roughly 40% of height variation in European ancestry populations and roughly 10-24% in other ancestries PMID 36224396. GTEx eQTL (expression quantitative trait locus, a variant associated with changes in how much a nearby gene is expressed) data show that the alternate allele at this locus is associated with reduced expression of the FBXL4 gene in esophageal and thyroid tissue GTEx Portal.

Reported associations

• Adult height: Identified as one of 12,111 independent height-associated SNPs in a GWAS of approximately 5.4 million individuals of diverse ancestries; no individual effect size for this specific variant is reported in the available study text PMID 36224396
• FBXL4 expression in esophagus gastroesophageal junction: The alternate allele is associated with reduced FBXL4 expression in this tissue (slope -0.15, p=8.9e-5) GTEx Portal
• FBXL4 expression in thyroid: The alternate allele is associated with reduced FBXL4 expression in thyroid tissue (slope -0.14, p=3.6e-6) GTEx Portal

Evidence quality The height association is drawn from a large-scale GWAS with approximately 5.4 million participants across five major ancestry groups, making it among the highest-powered genetic analyses of any common human trait PMID 36224396. The 12,111 height-associated SNPs identified together account for nearly all common SNP-based heritability for height in European ancestry populations. Prediction accuracy is substantially lower in non-European ancestry populations (roughly 10-24% of variance explained vs. 40-45% in European ancestry groups), which the authors attribute to differences in linkage disequilibrium (the tendency for nearby variants to be inherited together) and allele frequency rather than different underlying biology PMID 36224396. No individual p-value, beta coefficient, or effect size for rs12110525 specifically is available in the provided study text. The GTEx eQTL associations for FBXL4 are derived from GTEx v11 data (953 donors, FDR<0.05) and represent mechanistic tissue-level signals, not evidence of clinical outcomes.

Tissue-specific expression effects

• FBXL4: The alternate allele is associated with reduced expression in esophagus gastroesophageal junction tissue and in thyroid tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.