rs1049817 (GTF3C2): Lipid GWAS and Tissue eQTL
Key takeaways
- rs1049817 in GTF3C2 was examined in a lipidomic GWAS of 179 plasma lipid species in over 7,000 Finnish adults
- Common genetic variants near this gene were not found to be major drivers of sex differences in lipid profiles
- The alternate allele strongly increases GTF3C2-AS2 expression specifically in brain cerebellar tissue
- The same allele reduces SNX17 expression in skeletal muscle and affects multiple genes across brain, spleen, and thyroid
Key takeaways
- rs1049817 in GTF3C2 was examined in a lipidomic GWAS of 179 plasma lipid species in over 7,000 Finnish adults
- Common genetic variants near this gene were not found to be major drivers of sex differences in lipid profiles
- The alternate allele strongly increases GTF3C2-AS2 expression specifically in brain cerebellar tissue
- The same allele reduces SNX17 expression in skeletal muscle and affects multiple genes across brain, spleen, and thyroid
What the research says A sex-stratified genome-wide association study (GWAS) of 179 plasma lipid species in 7,266 Finnish participants (GeneRISK cohort), replicated in 2,045 additional participants, found significant sex differences in 141 lipid species (P<7.0x10^-4) and significant age-sex interactions in 121 species; the overall analysis concluded that common genetic variants do not play a major role in driving those sex differences. GTEx v11 data (953 donors) links rs1049817 to cis-expression quantitative trait locus (cis-eQTL) effects across several tissues, with particularly strong signals in brain cerebellar regions, skeletal muscle, and thyroid GTEx Portal.
Reported associations
- Plasma lipid species: rs1049817 was included in a sex-stratified lipidomic GWAS of 179 lipid species in 7,266 Finnish adults (GeneRISK cohort), replicated in 2,045 participants; the study's primary finding was that common genetic variants do not have a major role in sex differences in the lipidome, and no variant-specific effect size for this locus is available in the provided study text
- Gene expression - brain cerebellum: The alternate allele is associated with increased GTF3C2-AS2 expression in cerebellum (p=3.4e-39) and cerebellar hemisphere (p=1.3e-28) GTEx Portal
- Gene expression - skeletal muscle: The alternate allele is associated with reduced SNX17 expression in skeletal muscle (p=9.6e-78) GTEx Portal
- Gene expression - brain, spleen, thyroid: The alternate allele is associated with reduced ENSG00000295811 expression in anterior cingulate cortex (p=4.6e-22), hippocampus (p=1.0e-22), spleen (p=7.0e-21), and thyroid (p=1.9e-33) GTEx Portal
- Gene expression - testis: The alternate allele is associated with increased ENSG00000298520 expression in testis (p=1.5e-33) GTEx Portal
Evidence quality The lipidomic GWAS used a Finnish discovery cohort (n=7,266) with replication in 2,045 participants measured on the same shotgun lipidomics platform, providing moderate power for population-specific lipid genetics. The restriction to Finnish adults (GeneRISK cohort) may limit generalizability to other ancestries. No variant-specific effect sizes or p-values for rs1049817 in the lipid GWAS are available in the provided study text; the study's principal finding concerns the overall absence of major sex-specific genetic effects on the lipidome rather than any individual variant. GTEx eQTL evidence is well-powered across 953 donors, with all reported associations passing FDR<0.05; the skeletal muscle SNX17 signal (p=9.6e-78) and the brain cerebellar GTF3C2-AS2 signals (p=3.4e-39, p=1.3e-28) are among the strongest, while the thyroid, anterior cingulate cortex, hippocampus, spleen, and testis effects are also highly significant. These eQTL effects describe regulatory mechanisms and should not be interpreted as direct evidence of disease association.
Tissue-specific expression effects
- GTF3C2-AS2: The alternate allele is associated with increased expression in cerebellum (p=3.4e-39) and cerebellar hemisphere (p=1.3e-28) GTEx Portal
- SNX17: The alternate allele is associated with reduced expression in skeletal muscle (p=9.6e-78) GTEx Portal
- ENSG00000295811: The alternate allele is associated with reduced expression in anterior cingulate cortex (p=4.6e-22), hippocampus (p=1.0e-22), spleen (p=7.0e-21), and thyroid (p=1.9e-33) GTEx Portal
- ENSG00000298520: The alternate allele is associated with increased expression in testis (p=1.5e-33) GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs1049817?
rs1049817 is a genetic variant in the GTF3C2 gene region. It has been studied in a genome-wide analysis of plasma lipid species and is linked in GTEx data to gene expression changes across several tissues including brain, skeletal muscle, and thyroid.
What lipid traits is rs1049817 associated with?
rs1049817 was included in a sex-stratified genome-wide association study of 179 plasma lipid species in over 7,000 Finnish adults. The study found that common variants as a whole do not majorly drive sex differences in lipid levels, and no specific effect size for this variant was reported in the available text.
What does GTEx data show for rs1049817?
GTEx v11 data (953 donors) shows rs1049817 increases expression of GTF3C2-AS2 in brain cerebellar regions and increases expression of another gene in testis, while reducing expression of SNX17 in skeletal muscle and reducing a separate gene in anterior cingulate cortex, hippocampus, spleen, and thyroid. All signals passed FDR less than 0.05.
Is rs1049817 linked to brain function?
GTEx data links rs1049817 to gene expression changes in multiple brain regions including the cerebellum and hippocampus. These are regulatory gene expression associations and do not directly measure brain function or disease risk.
What is GTF3C2-AS2?
GTF3C2-AS2 is a gene located near GTF3C2 whose expression is strongly increased by the alternate allele of rs1049817 in brain cerebellar tissue according to GTEx v11. Its broader biological role in this context has not been characterized in the available research.