rs10509543 (RNLS): Height and Gene Expression Variant

Key takeaways

• rs10509543 is one of 12,111 common variants significantly linked to adult height in a genome-wide association study of 5.4 million people.
• The alternate allele at this locus reduces RNLS gene activity in at least five different body tissues, including thyroid and skeletal muscle.
• The alternate allele also increases LIPJ expression in skeletal muscle while reducing RNLS expression in the same tissue.
• Height associations at this scale explain about 40% of height variation in people of European ancestry, but considerably less in other ancestry groups.

What the research says rs10509543 is among the 12,111 independent SNPs (single-nucleotide polymorphisms, meaning single-letter DNA changes) identified as significantly associated with adult height in a genome-wide association study (GWAS) of 5,380,080 individuals from 281 studies spanning five ancestral groups PMID 36198281. These SNPs cluster within 7,209 non-overlapping genomic segments covering roughly 21% of the genome and collectively account for approximately 40% of height-related phenotypic variance (45% when all HapMap 3 reference panel SNPs are used) in populations of European ancestry, dropping to 10-20% in other ancestry groups PMID 36198281. GTEx v11 expression data (953 donors, FDR below 5%) further shows that the alternate allele at this locus is associated with reduced expression of RNLS (ENSG00000306542) across five tissue types and with increased LIPJ expression in skeletal muscle GTEx Portal.

Reported associations

• Adult height: one of 12,111 independent significant SNPs in a GWAS of 5,380,080 individuals from 281 studies spanning five ancestry groups PMID 36198281
• RNLS expression in thyroid: alternate allele associated with reduced expression (p=4.6e-9) GTEx Portal
• RNLS expression in breast mammary tissue: alternate allele associated with reduced expression (p=4.9e-5) GTEx Portal
• RNLS expression in tibial nerve: alternate allele associated with reduced expression (p=2.8e-5) GTEx Portal
• RNLS expression in skeletal muscle: alternate allele associated with reduced expression (p=1.1e-10) GTEx Portal
• RNLS expression in subcutaneous adipose tissue: alternate allele associated with reduced expression (p=6.4e-5) GTEx Portal
• LIPJ expression in skeletal muscle: alternate allele associated with increased expression (p=2.4e-5) GTEx Portal

Evidence quality The height association rests on one of the largest genetic discovery samples assembled (n=5,380,080 across 281 studies), with the 12,111 significant SNPs together explaining roughly 40% of phenotypic variance in populations of European ancestry and 10-20% in other ancestry groups PMID 36198281. The authors attribute reduced prediction accuracy in non-European populations to differences in linkage disequilibrium (the tendency of nearby genetic variants to be inherited together) and allele frequencies rather than different causal biology, noting that effect sizes and associated regions are broadly consistent across groups PMID 36198281. The GTEx eQTL (expression quantitative trait locus, a variant that affects how much a nearby gene is expressed) associations are derived from 953 donors at a false discovery rate below 5% and represent mechanistic context only, not clinical outcome data. No conflicting findings are present in the provided sources.

Tissue-specific expression effects

• RNLS: the alternate allele is associated with reduced expression in thyroid, breast mammary tissue, tibial nerve, skeletal muscle, and subcutaneous adipose tissue GTEx Portal
• LIPJ: the alternate allele is associated with increased expression in skeletal muscle GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.