Expressive

rs10411195 (ZNF93): Smoking Behavior and Brain Expression

Key takeaways

  • rs10411195 is near ZNF93 and was examined in a genome-wide study of cigarette smoking behaviors involving about 4,600 participants
  • No variant in the study reached genome-wide significance, placing any smoking-behavior link in the preliminary range
  • The alternate allele links to increased ZNF93 expression in the cerebellar hemisphere and putamen, two brain regions tied to motor control and reward
  • The same variant reduces expression of a nearby pseudogene (ZNF56P) in fibroblasts and muscle
  • Effect sizes for brain expression were moderate, with the strongest signal in the cerebellar hemisphere (slope +0.65)

Key takeaways

  • rs10411195 is located near ZNF93 (a zinc finger protein gene) and was examined in a genome-wide association study of cigarette smoking behaviors involving approximately 4,600 participants
  • No variant in the study reached genome-wide significance, placing any smoking-behavior link for this variant in the preliminary, sub-threshold range
  • GTEx tissue expression data from 953 donors link the alternate allele to increased ZNF93 expression in the cerebellar hemisphere and putamen, brain regions involved in motor coordination and reward processing
  • The same variant is also associated with decreased expression of ZNF56P, a nearby pseudogene, in cultured fibroblasts and skeletal muscle
  • Effect sizes for ZNF93 brain expression were moderate in magnitude (slope +0.65 in cerebellar hemisphere, +0.48 in putamen basal ganglia)

What the research says A genome-wide association study (a large-scale scan comparing genetic variants across many individuals to identify statistical links to traits) analyzed seven measures of cigarette smoking behavior, including cigarettes per day, age at initiation, duration, pack years, ever/never status, smoking intensity category, and current-versus-former status, in 2,329 men from the Prostate, Lung, Colon and Ovarian Trial and 2,282 women from the Nurses' Health Study; no variant in the combined analysis reached genome-wide significance, and between two and seven variants per measure reached the lower suggestive threshold of p less than one in one hundred thousand. Independent tissue expression data from GTEx v11 (953 donors, false discovery rate below 0.05) show that the alternate allele at this locus is associated with increased ZNF93 expression in the cerebellar hemisphere (slope +0.65, p=3.0e-6), putamen basal ganglia (+0.48, p=3.0e-5), skeletal muscle (+0.39, p=8.4e-5), and thyroid (+0.35, p=3.1e-5), and with decreased expression of ZNF56P (a nearby pseudogene) in cultured fibroblasts (-0.33, p=4.4e-5) and skeletal muscle (-0.31, p=2.2e-4) GTEx Portal. A third nearby zinc finger gene, ZNF253, shows increased expression in tibial nerve (slope +0.30, p=1.2e-4) and cerebellar hemisphere (+0.27, p=1.4e-4) at this variant GTEx Portal.

Reported associations

  • Cigarette smoking behaviors (seven measures): Analyzed in a GWAS of cigarettes per day, age at initiation, smoking duration, pack years, ever/never status, intensity category, and current-versus-former status across approximately 4,600 participants; no genome-wide significant association was observed for any variant in the combined analysis
  • ZNF93 gene expression: The alternate allele associates with increased ZNF93 expression in the cerebellar hemisphere (slope +0.65), putamen basal ganglia (+0.48), skeletal muscle (+0.39), and thyroid (+0.35) GTEx Portal
  • ZNF56P expression (pseudogene): The alternate allele associates with decreased expression of this nearby pseudogene in cultured fibroblasts (slope -0.33) and skeletal muscle (-0.31) GTEx Portal
  • ZNF253 gene expression: The alternate allele associates with increased ZNF253 expression in tibial nerve (slope +0.30) and cerebellar hemisphere (+0.27) GTEx Portal

Evidence quality The smoking behavior GWAS included approximately 4,600 participants drawn from two independent cohorts (the PLCO trial and the Nurses' Health Study), a sample size considered modest by current genome-wide standards. No genome-wide significant associations were reported in the combined analysis, meaning any smoking-behavior link for rs10411195 is sub-threshold and preliminary; the study authors explicitly stated that sub-threshold results required further follow-up. The parallel analysis of 11,199 SNPs across 359 candidate genes corrected for multiple tests within each gene, and the replication of the chromosome 15q25.1 nicotinic receptor region (CHRNA3 and CHRNA5) lends methodological credibility to the overall study design. The GTEx eQTL evidence is drawn from 953 donors across multiple tissues at a false discovery rate (FDR, a measure of how many false positives are expected among statistically significant results) below 0.05, providing a more robust signal for ZNF93 expression effects, though eQTL associations describe gene regulation rather than direct disease outcomes GTEx Portal. No conflicting findings between the GWAS and eQTL data were identified, though the two data types address distinct biological questions.

Tissue-specific expression effects

  • ZNF93: Increased expression in the cerebellar hemisphere (a brain region involved in motor coordination and precision) and the putamen (a basal ganglia structure involved in reward processing, motor learning, and habit formation), as well as in skeletal muscle and thyroid; the largest effect is in cerebellar tissue GTEx Portal
  • ZNF56P: Reduced expression in cultured fibroblasts and skeletal muscle GTEx Portal
  • ZNF253: Increased expression in tibial nerve and cerebellar hemisphere GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is ZNF93 and what does it do?

ZNF93 is a zinc finger protein gene, a class of genes that produce proteins involved in regulating the activity of other genes. Its specific biological roles in human health are not fully characterized in the available research.

Is rs10411195 linked to cigarette smoking?

rs10411195 was analyzed in a genome-wide association study of cigarette smoking behaviors, but no variant in that study reached genome-wide significance in the combined analysis. Any connection to smoking behavior is considered preliminary and has not been confirmed at the standard significance threshold.

Which brain regions show expression changes linked to rs10411195?

GTEx data from 953 donors show the alternate allele is associated with increased ZNF93 expression in the cerebellar hemisphere and the putamen basal ganglia, regions involved in motor coordination, reward, and habit formation. These are gene expression observations, not direct measures of brain function or behavior.

What other genes are affected by rs10411195?

GTEx data show this variant is also associated with decreased expression of ZNF56P, a nearby pseudogene, in fibroblasts and skeletal muscle, and with increased expression of ZNF253, another zinc finger gene, in tibial nerve and cerebellar hemisphere.

How strong is the evidence for rs10411195?

The smoking behavior GWAS covered about 4,600 participants and found no genome-wide significant findings, making any smoking link preliminary. The GTEx expression data are from 953 donors across multiple tissues at a false discovery rate below 0.05, providing a statistically more robust signal for gene expression effects, though expression data do not directly imply disease risk.