rs1018466 (NKX2-1-AS1): Height Genetics Variant
Key takeaways
- Identified as one of 12,111 height-associated variants in a genome-wide study of 5.4 million people across diverse ancestries
- The alternate allele increases expression of ENSG00000258661 and PAX9 in thyroid tissue
- The alternate allele also increases PAX9 expression in tibial artery
- The alternate allele reduces NKX2-8 expression in esophageal mucosa
- No clinical outcome or lifestyle data are currently available for this specific variant
Key takeaways
- Identified as one of 12,111 height-associated variants in a genome-wide study of 5.4 million people across diverse ancestries
- The alternate allele increases expression of ENSG00000258661 and PAX9 in thyroid tissue
- The alternate allele also increases PAX9 expression in tibial artery
- The alternate allele reduces NKX2-8 expression in esophageal mucosa
- No clinical outcome or lifestyle data are currently available for this specific variant
What the research says A genome-wide association study (GWAS, a large scan of genetic variants across millions of people) of 5.4 million individuals from 281 studies across five ancestry groups identified 12,111 independent SNPs (single-nucleotide polymorphisms, single-letter DNA changes) significantly associated with adult height, including rs1018466 at the NKX2-1-AS1 locus. These 12,111 variants collectively account for approximately 40 percent of height variance in European-ancestry populations (or approximately 45 percent when all variants in the HapMap 3 reference panel are considered). Tissue expression data show that the alternate allele at this locus increases expression of ENSG00000258661 and PAX9 in thyroid tissue and PAX9 in tibial artery, and reduces NKX2-8 expression in esophageal mucosa GTEx Portal.
Reported associations
- Adult height: Identified as one of 12,111 genome-wide significant height-associated SNPs in a GWAS of 5.4 million participants; individual effect size for this single variant was not separately reported in the study
- ENSG00000258661 expression in thyroid: the alternate allele is linked to increased expression (slope +0.34 log2-normalized units, p=7.3e-12) in thyroid tissue GTEx Portal
- PAX9 expression in thyroid: the alternate allele is linked to increased PAX9 expression (slope +0.33, p=2.0e-11) in thyroid tissue GTEx Portal
- PAX9 expression in tibial artery: the alternate allele is also linked to increased PAX9 expression (slope +0.14, p=8.9e-6) in tibial artery GTEx Portal
- NKX2-8 expression in esophageal mucosa: the alternate allele is linked to reduced NKX2-8 expression (slope -0.19, p=6.7e-9) in the mucosa lining the esophagus GTEx Portal
Evidence quality The height association derives from one of the largest GWASs published to date, covering approximately 5.4 million participants across 281 studies and five broad ancestry groups (European 75.8%, East Asian 8.8%, Hispanic 8.5%, African 5.5%, South Asian 1.4%). The study achieved near-saturation of height-associated common variants in European-ancestry populations but notes that prediction accuracy is substantially lower in non-European populations, likely due to differences in linkage disequilibrium (the tendency of nearby genetic variants to be inherited together) and allele frequency patterns. No variant-specific p-value or effect size for rs1018466 alone was provided in the available study text. The GTEx eQTL (expression quantitative trait locus, meaning a variant that predicts how much of a gene is produced in a given tissue) data are based on 953 donors with a false discovery rate below 0.05, supporting moderate to strong statistical evidence for the reported expression effects. These eQTL findings describe a biological mechanism and do not directly establish causal pathways to height or any clinical outcome.
Tissue-specific expression effects
- ENSG00000258661: the alternate allele is linked to increased expression in thyroid tissue GTEx Portal
- PAX9: the alternate allele is linked to increased expression in both thyroid tissue and tibial artery GTEx Portal
- NKX2-8: the alternate allele is linked to reduced expression in the mucosa lining the esophagus GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs1018466?
rs1018466 is a common genetic variant located near the NKX2-1-AS1 gene. It is one of 12,111 variants genome-wide significantly associated with adult human height, identified in a study of 5.4 million people.
What is NKX2-1-AS1?
NKX2-1-AS1 is a gene region linked to adult height in large genetic studies. Variants in this area are also associated with changes in the expression of nearby genes, including PAX9 and NKX2-8, in tissues such as the thyroid and esophagus.
Is rs1018466 linked to height?
Yes. A genome-wide association study of 5.4 million people identified rs1018466 as one of 12,111 variants significantly associated with adult height. The individual effect size for this specific variant alone was not separately reported in the study.
What tissues are affected by rs1018466?
GTEx tissue expression data show that the alternate allele at rs1018466 increases expression of ENSG00000258661 and PAX9 in thyroid tissue, increases PAX9 expression in tibial artery, and reduces NKX2-8 expression in esophageal mucosa.
How strong is the evidence for rs1018466?
The height association comes from a very large GWAS of approximately 5.4 million people, providing strong statistical power. The tissue expression data come from GTEx with 953 donors and a false discovery rate below 0.05. No clinical outcome studies specific to this variant have been identified in the current evidence base.