rs1001098 (TNS1): Common height and expression variant

Key takeaways

• rs1001098 is one of 12,111 common genetic variants significantly associated with adult height, identified in a genome-wide study of 5.4 million people across diverse ancestries.
• These height-associated variants together explain about 40% of height differences in people of European ancestry, and 10-20% in other ancestries.
• The variant is linked to reduced expression of the TNS1 gene in lab-grown fibroblast cells, based on GTEx tissue expression data.
• The same variant is associated with increased expression of the RUFY4 gene in lung tissue.
• These are population-level findings; rs1001098 is one of thousands of variants influencing a complex trait.

What the research says A genome-wide association study (a large scan comparing single-letter DNA differences across many people's genomes, abbreviated GWAS) of 5.4 million individuals from 281 contributing studies identified 12,111 independent common SNPs (single-nucleotide polymorphisms, meaning single-letter DNA changes) significantly associated with adult height, with rs1001098 implicated as one of these variants. These SNPs collectively explain roughly 40% of height variation in populations of European ancestry and approximately 10-20% in other ancestries, a gap attributed to differences in linkage disequilibrium (the tendency of nearby DNA variants to be inherited together) and allele frequency (how common each variant form is) across populations. Tissue-specific gene expression data shows that the alternate form of this variant is linked to reduced expression of the TNS1 gene in lab-grown fibroblast cells and increased expression of the RUFY4 gene in lung tissue GTEx Portal.

Reported associations

• Adult height: Identified as one of 12,111 independent SNPs significantly associated with adult height in a multi-ancestry GWAS of 5.4 million individuals from 281 studies, covering participants of European, East Asian, Hispanic, African, and South Asian ancestries.
• TNS1 expression in lab-grown fibroblast cells: The alternate allele (the non-reference DNA form at this genomic position) is associated with reduced expression of TNS1 in cultured fibroblast cells (p=2.1e-4, 953 GTEx v11 donors) GTEx Portal.
• RUFY4 expression in lung tissue: The alternate allele is associated with increased expression of RUFY4 in lung tissue (p=5.7e-5, 953 GTEx v11 donors) GTEx Portal.

Evidence quality The height association is drawn from one of the largest genetic studies conducted, covering 5.4 million individuals across 281 contributing studies. The 12,111 identified SNPs are predicted to account for nearly all common SNP-based heritability for height, with associated segments covering roughly 21% of the genome. No individual effect size for rs1001098 alone is reported in the summary data available here. The evidence is strongest for European-ancestry populations; the same variants explain substantially less height variation in other ancestry groups, a recognized limitation attributed to differences in the structure of genetic variation across populations. The GTEx eQTL results (eQTL, or expression quantitative trait locus, refers to a variant that influences gene activity levels) for TNS1 in cultured fibroblasts (p=2.1e-4) and RUFY4 in lung (p=5.7e-5) meet the FDR threshold applied by GTEx v11 across 953 donors. Expression effect sizes are modest (log2-normalized slopes of -0.11 for TNS1 and +0.20 for RUFY4), and eQTL findings reflect mechanisms of gene regulation rather than direct disease outcomes.

Tissue-specific expression effects

• TNS1: The alternate allele is associated with reduced expression in lab-grown fibroblast cells GTEx Portal.
• RUFY4: The alternate allele is associated with increased expression in lung tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.