Expressive

rs10801696 (KYAT3): Metabolite & Brain Expression

Key takeaways

  • rs10801696 at the KYAT3 locus was identified in a GWAS of 722 metabolites in 8,809 European adults.
  • The alternate allele is associated with increased KYAT3 expression in four brain regions, including cortex and nucleus accumbens.
  • The strongest expression signal appears in cultured fibroblasts (p = 9.8 x 10^-160), with increases also in skeletal muscle, tibial nerve, and testis.
  • These are gene-expression findings, not clinical diagnoses or health outcome predictions.

Key takeaways

  • rs10801696, at the KYAT3 locus, was identified in a large genome-wide study of 722 circulating metabolite levels in 8,809 European adults.
  • The alternate allele is associated with increased KYAT3 expression in four brain regions: cortex, frontal cortex, nucleus accumbens, and anterior cingulate cortex.
  • The strongest single-tissue expression signal at this variant appears in cultured fibroblasts (p = 9.8 x 10^-160), with additional increases in skeletal muscle, tibial nerve, and testis.
  • These are molecular findings about gene expression and metabolite levels, not clinical diagnoses or health outcomes.

What the research says A genome-wide association study (GWAS) of 722 circulating metabolite levels in 8,809 European adults identified 202 unique genomic regions, including 74 novel regions, associated with 478 metabolites; these associations were replicated in an independent cohort of 1,768 Europeans. GTEx v11 expression data (953 donors) show the alternate allele at rs10801696 is strongly associated with increased KYAT3 expression across multiple brain regions and peripheral tissues, with effect sizes (slopes) ranging from +0.41 to +0.84 log2-normalized expression units GTEx Portal.

Reported associations

  • Circulating metabolite levels: rs10801696 is located at the KYAT3 locus, identified within a GWAS of 722 metabolites in 8,809 Europeans; the study catalogued 202 genomic regions associated with 478 metabolites, including 74 novel loci not previously listed in the GWAS Catalog, with replication in 1,768 additional individuals.
  • KYAT3 expression (multiple tissues): GTEx v11 data link the alternate allele to increased KYAT3 expression across eight tissues, with effect slopes ranging from +0.41 (skeletal muscle, tibial nerve) to +0.84 (brain cortex) GTEx Portal.

Evidence quality The metabolomics GWAS applied a genome-wide significance threshold of p < 6.92 x 10^-11 (the standard p < 5 x 10^-8 adjusted for 722 parallel tests) across more than 10 million HRC-imputed genetic markers. Low genomic inflation factors were reported across all analyses, indicating no major population-stratification artifacts. Findings were replicated in an independent European sample of 1,768 individuals. GTEx eQTL associations for KYAT3 at this locus are well below FDR < 0.05 in all eight reported tissues, with p-values as low as 9.8 x 10^-160 in fibroblasts and 1.1 x 10^-35 in anterior cingulate cortex GTEx Portal. These eQTL signals describe differences in gene expression by genotype and represent mechanistic rather than clinical outcome data. No conflicting findings are present across the available sources.

Tissue-specific expression effects

  • KYAT3: The alternate allele is associated with increased expression in brain cortex (+0.84 log2 units, p = 9.9 x 10^-48), nucleus accumbens basal ganglia (+0.77, p = 2.3 x 10^-53), frontal cortex BA9 (+0.77, p = 1.9 x 10^-42), anterior cingulate cortex BA24 (+0.72, p = 1.1 x 10^-35), cultured fibroblasts (+0.72, p = 9.8 x 10^-160), testis (+0.53, p = 1.3 x 10^-82), tibial nerve (+0.41, p = 1.7 x 10^-75), and skeletal muscle (+0.41, p = 7.5 x 10^-54) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10801696?

rs10801696 is a genetic variant at the KYAT3 gene locus. It has been studied in genome-wide association research on circulating metabolite levels and shows strong associations with KYAT3 gene expression across multiple tissues in GTEx data.

What does rs10801696 affect?

rs10801696 is located at the KYAT3 locus, identified in a GWAS of 722 metabolite levels in 8,809 European adults. GTEx data show the alternate allele is associated with increased KYAT3 expression in multiple brain regions, skeletal muscle, tibial nerve, testis, and fibroblasts.

Is rs10801696 linked to brain gene activity?

GTEx expression data show the alternate allele at rs10801696 is associated with increased KYAT3 gene expression in brain cortex, frontal cortex, nucleus accumbens, and anterior cingulate cortex. These are gene-expression findings and do not directly establish links to brain behavior or clinical conditions.

How reliable is the evidence for rs10801696?

The GWAS used over 10 million genetic markers across 8,809 Europeans with replication in 1,768 additional individuals. The GTEx eQTL p-values range from 9.8 x 10^-160 to 1.1 x 10^-35 across eight tissues, all well below standard significance thresholds. Evidence at the molecular level is robust, but clinical interpretation requires additional research.

Is rs10801696 associated with any disease?

The studies available here do not link rs10801696 to any specific disease. Reported associations are with circulating metabolite levels and with KYAT3 gene expression in various tissues.