rs11130605 (FLNB): Common Height-Linked Variant

Key takeaways

• rs11130605 is one of 12,111 common variants significantly linked to adult height in a genome-wide association study of 5.4 million people
• The full set of 12,111 height variants explains roughly 40% of height variation in people of European ancestry (45% when using all HapMap 3 reference panel variants)
• GTEx data links this variant to tissue-specific changes in FLNB and nearby gene expression, with the direction of effect varying by gene and tissue
• Prediction accuracy from these variants is lower in non-European populations (roughly 10-20% variance explained vs. 40%), though effect sizes appear consistent across ancestries

What the research says rs11130605 was identified as one of 12,111 independent SNPs (single-nucleotide polymorphisms, meaning single-letter DNA variants) significantly associated with adult height in a GWAS (genome-wide association study) of 5.4 million individuals across diverse ancestries PMID 36224396. These variants fall within 7,209 non-overlapping genomic segments covering roughly 21% of the genome and together account for nearly all common SNP-based heritability of height PMID 36224396. In populations of European ancestry, the 12,111 SNPs account for 40% of phenotypic variance in height (45% when using all HapMap 3 panel variants), while that figure drops to approximately 10-20% (14-24%) in non-European populations PMID 36224396.

Reported associations

• Adult height: Identified as one of 12,111 genome-wide significant height-associated variants in a GWAS of 5.4 million individuals; the 12,111 SNPs collectively account for nearly all common SNP-based heritability of height PMID 36224396

Evidence quality The source GWAS by Yengo et al. (2022) is one of the largest genetic studies ever conducted, with 5.4 million participants across 281 studies spanning five broad ancestry groups: predominantly European (75.8%), East Asian (8.8%), Hispanic (8.5%), African (5.5%), and South Asian (1.4%) PMID 36224396. The 12,111 variants identified represent a near-saturation of common variant associations with height in European-ancestry populations, as the study authors conclude PMID 36224396. No individual p-value or per-allele effect size for rs11130605 specifically is reported in the available study text; the evidence for this locus is contextualized within the broader multi-million-person discovery rather than as an isolated finding PMID 36224396. Effect sizes and associated genomic regions were found to be broadly similar across ancestries, though reduced prediction accuracy in non-European populations is attributed to differences in linkage disequilibrium (the tendency for nearby variants to be co-inherited) and allele frequency distributions PMID 36224396.

Tissue-specific expression effects

• FLNB: The alternative allele is associated with reduced expression in cultured fibroblasts (connective tissue cells) and increased expression in tibial nerve tissue GTEx Portal
• FLNB-AS1 (an antisense RNA transcript associated with the FLNB gene): The alternative allele is associated with reduced expression in cultured fibroblasts GTEx Portal
• PXK: The alternative allele is associated with increased expression in tibial nerve tissue and visceral adipose (abdominal fat) tissue GTEx Portal
• RPP14: The alternative allele is associated with reduced expression in heart left ventricle and skeletal muscle GTEx Portal
• ARF4: The alternative allele is associated with increased expression in cultured fibroblasts GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.