Expressive

rs1063739 (GPT): Blood gene expression variant

Key takeaways

  • rs1063739, a variant in the GPT gene region, was identified in the VA Million Veteran Program, one of the largest and most diverse US genetic studies, covering 2,068 traits in 635,969 participants across four population groups
  • The alternative allele consistently reduces expression of PPP1R16A across blood, spleen, lymphocytes, and esophageal tissue, with the whole blood signal among the most statistically significant eQTL effects in the GTEx dataset
  • LRRC14 expression is also reduced in blood and lymphocytes, suggesting coordinated regulatory effects in immune-related tissues
  • This locus is associated with increased KIFC2 expression in thyroid tissue and reduced expression of an uncharacterized gene in testis, indicating tissue-specific regulatory reach beyond the immune system
  • More than 3,400 associations in the underlying GWAS were detectable only when non-European participants were included, highlighting how population diversity expands genetic discovery

Key takeaways

  • rs1063739, a variant in the GPT gene region, was identified in the VA Million Veteran Program, one of the largest and most diverse US genetic studies, covering 2,068 traits in 635,969 participants across four population groups
  • The alternative allele consistently reduces expression of PPP1R16A across blood, spleen, lymphocytes, and esophageal tissue, with the whole blood signal among the most statistically significant eQTL effects in the GTEx dataset
  • LRRC14 expression is also reduced in blood and lymphocytes, suggesting coordinated regulatory effects in immune-related tissues
  • This locus is associated with increased KIFC2 expression in thyroid tissue and reduced expression of an uncharacterized gene in testis, indicating tissue-specific regulatory reach beyond the immune system
  • More than 3,400 associations in the underlying GWAS were detectable only when non-European participants were included, highlighting how population diversity expands genetic discovery

What the research says The VA Million Veteran Program (MVP) conducted genome-wide association studies (a method that scans millions of genetic variants across the genome to find those associated with traits or conditions) across 2,068 traits in 635,969 participants from four genetically diverse population groups: African, Admixed American, East Asian, and European. The study identified 26,049 variant-trait associations across 1,270 traits, with fine-mapping (a statistical method that narrows a broadly associated genomic region down to the most likely causal variant) resolving 57,601 independent signals across 936 traits, of which 15,045 were mapped with high confidence to a single variant. Notably, 3,477 of these associations were significant only after including non-European participants, illustrating how population diversity substantially expands discovery in large-scale genetic research.

Reported associations

  • Multi-population GWAS context: This variant falls within the scope of the MVP study covering 2,068 traits in 635,969 diverse US Veterans; trait-specific association data for this variant are not enumerated in the available study text
  • PPP1R16A expression, whole blood: the alternative allele reduces PPP1R16A expression in whole blood with very high statistical significance (p=2.7e-54, 953 donors) GTEx Portal
  • PPP1R16A expression, spleen: reduced expression (p=4.9e-23) GTEx Portal
  • PPP1R16A expression, lymphocytes: reduced expression in EBV-transformed lymphocytes (immune cells adapted for laboratory culture, p=4.2e-21) GTEx Portal
  • PPP1R16A expression, esophagus mucosa: reduced expression (p=2.5e-21) GTEx Portal
  • LRRC14 expression, lymphocytes: reduced LRRC14 expression in EBV-transformed lymphocytes (p=1.7e-23) GTEx Portal
  • LRRC14 expression, whole blood: reduced expression (p=4.7e-22) GTEx Portal
  • KIFC2 expression, thyroid: increased KIFC2 expression in thyroid tissue (p=1.3e-17) GTEx Portal
  • ENSG00000301017 expression, testis: reduced expression of this uncharacterized gene in testis (p=2.7e-11) GTEx Portal

Evidence quality The GWAS context for this variant comes from the VA MVP study (Verma et al., Science 2024), which enrolled 635,969 participants from four population groups and applied statistical fine-mapping to prioritize causal variants, making it among the most statistically powerful and ethnically diverse GWAS cohorts conducted to date. Trait-specific effect sizes for rs1063739 are not available in the provided text. GTEx v11 eQTL data (an eQTL, or expression quantitative trait locus, is a genetic variant that influences how active a nearby gene is; 953 donors, false discovery rate FDR below 0.05, analysis restricted to variants in the genomic neighborhood of each gene) provides strong statistical support for the regulatory effects described here. The PPP1R16A whole blood signal (p=2.7e-54) is exceptionally strong by any standard. Multi-tissue replication across four independent tissues for PPP1R16A and two tissues for LRRC14 substantially increases confidence in those regulatory effects. The ENSG00000301017 and KIFC2 signals each rest on single-tissue evidence only and should be considered preliminary pending further replication.

Tissue-specific expression effects

  • PPP1R16A: reduced expression in whole blood (p=2.7e-54), spleen, EBV-transformed lymphocytes, and esophagus mucosa; four-tissue replication across immune and hematopoietic (blood-forming) tissues strengthens confidence in this regulatory association GTEx Portal
  • LRRC14: reduced expression in whole blood and EBV-transformed lymphocytes; two-tissue replication consistent with a role in immune and blood-forming tissues GTEx Portal
  • ENSG00000301017: reduced expression in testis only; single-tissue evidence, preliminary GTEx Portal
  • KIFC2: increased expression in thyroid tissue only; single-tissue evidence, preliminary GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs1063739?

rs1063739 is a common genetic variant located near the GPT gene. It is associated with changes in gene activity across blood, spleen, lymphocytes, and other tissues based on data from hundreds of donors in the GTEx reference dataset.

What genes does rs1063739 affect?

Based on GTEx tissue expression data from 953 donors, this variant reduces expression of PPP1R16A across four tissues and LRRC14 in two tissues. It also increases KIFC2 expression in thyroid and reduces expression of an uncharacterized gene (ENSG00000301017) in testis.

Why is the blood gene-expression effect of rs1063739 considered strong?

The effect on PPP1R16A expression in whole blood reaches p=2.7e-54 in GTEx data, which is exceptionally significant. The same direction of effect appears independently in spleen and lymphocytes as well, pointing to a robust regulatory role across immune and blood-forming tissues.

Was rs1063739 identified in a major genetic study?

This variant was identified in the scope of the VA Million Veteran Program, one of the largest and most ethnically diverse GWAS projects in the US, which analyzed 2,068 traits across 635,969 participants from African, Admixed American, East Asian, and European population groups.

Is rs1063739 linked to a specific disease?

Specific disease associations for this variant are not detailed in the available research text. The GTEx data describes changes in gene expression levels across tissues, which are mechanistic findings about gene regulation and do not on their own indicate disease risk.