Expressive

rs1124742 (PDE8B): Tobacco, Alcohol & Brain Expression

Key takeaways

  • Found in a genome-wide study of 3.4 million people examining tobacco and alcohol use behaviors
  • The alternate allele increases WDR41 gene expression in brain, skin, and esophageal tissues across seven tissue types
  • The same alternate allele decreases PDE8B expression in the cerebellar hemisphere of the brain
  • PDE8B encodes phosphodiesterase 8B, an enzyme involved in breaking down cyclic AMP, a key cellular signaling molecule
  • Specific behavioral phenotype and per-variant effect size are not detailed in the available study text

Key takeaways

  • rs1124742 is a genetic variant in the PDE8B gene region, identified in a large multi-ancestry genome-wide study of tobacco and alcohol use behaviors
  • The variant's alternate allele is linked to increased expression of WDR41 in brain (cerebellum and hippocampus), skin, and esophageal tissues
  • The same alternate allele is linked to decreased PDE8B (phosphodiesterase 8B) expression in the brain's cerebellar hemisphere
  • The genome-wide study that identified this locus enrolled approximately 3.4 million participants from diverse ancestry backgrounds, with about 21% from non-European populations
  • Specific phenotype assignment and per-variant effect size for rs1124742 are not reported in the available study text, which limits interpretation

What the research says rs1124742 was reported in a large multi-ancestry genome-wide association study (GWAS) of tobacco and alcohol use behaviors (Saunders et al., Nature 2023), which analyzed approximately 3.4 million individuals from diverse global ancestry groups, with roughly 21% from non-European backgrounds. The study examined five behavioral phenotypes: smoking initiation, age at smoking onset, cigarettes smoked per day, smoking cessation, and drinks per week. Expression quantitative trait locus (eQTL) data from GTEx v11 show that the alternate allele at this locus is associated with increased expression of the nearby WDR41 gene (WD repeat domain 41) in brain, skin, and esophageal tissues, and with decreased expression of PDE8B (phosphodiesterase 8B, an enzyme that degrades cyclic AMP, a key cellular signaling molecule) in the brain's cerebellar hemisphere GTEx Portal.

Reported associations

  • Tobacco and/or alcohol use phenotype(s): this locus was identified within a multi-ancestry GWAS examining five phenotypes related to smoking and alcohol consumption in up to 3.4 million participants; the specific phenotype and per-variant effect size for rs1124742 are not specified in the available study text
  • WDR41 expression (eQTL): the alternate allele is associated with increased WDR41 expression in brain cerebellum (effect size +0.35 log2-normalized units), brain hippocampus (+0.24), unexposed skin (+0.21), sun-exposed skin (+0.19), esophageal mucosa (+0.19), esophageal muscularis (+0.17), and cultured fibroblasts (+0.12) GTEx Portal
  • PDE8B expression (eQTL): the alternate allele is associated with decreased PDE8B expression in brain cerebellar hemisphere tissue (effect size -0.23 log2-normalized units) GTEx Portal

Evidence quality The GWAS source is large and methodologically robust, enrolling approximately 3.4 million participants from multiple ancestry groups (roughly 21% non-European) and applying a multi-ancestry meta-regression approach designed to detect consistent effects across populations while accounting for per-study axes of genetic ancestry variation. The study identified 2,143 associated loci in total across all five phenotypes. GTEx eQTL associations (GTEx v11, n=953 donors) meet a false discovery rate threshold of less than 0.05, and the WDR41 eQTL signals span seven tissue types, which strengthens confidence in that expression effect. The behavioral GWAS evidence and the eQTL evidence are mechanistically distinct and no conflicting findings were identified across the provided data. Because the specific phenotype and per-variant effect size for rs1124742 are not reported in the available study text, the behavioral association cannot be fully characterized from these materials alone, and this entry treats that gap as a limitation.

Tissue-specific expression effects

  • WDR41: the alternate allele is associated with increased expression in brain cerebellum, brain hippocampus, unexposed and sun-exposed skin, esophageal mucosa and muscularis, and cultured fibroblasts GTEx Portal
  • PDE8B: the alternate allele is associated with reduced expression in brain cerebellar hemisphere tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What gene is rs1124742 in?

rs1124742 is located in or near the PDE8B gene, which encodes phosphodiesterase 8B, an enzyme that breaks down cyclic AMP, a molecule involved in many cellular signaling processes.

What is rs1124742 associated with?

This variant was identified in a large genome-wide study of tobacco and alcohol use behaviors across 3.4 million participants. It is also linked to changes in how the nearby genes WDR41 and PDE8B are expressed in brain and other tissues.

What does the PDE8B gene do?

PDE8B (phosphodiesterase 8B) encodes an enzyme that breaks down cyclic AMP, a molecule that helps cells respond to hormonal and neurochemical signals. It is active in multiple tissues, including the brain.

Does rs1124742 affect brain gene expression?

Yes. Expression data from GTEx v11 show the alternate allele of rs1124742 is linked to reduced PDE8B expression in the cerebellar hemisphere and increased WDR41 expression in the cerebellum and hippocampus.

Is rs1124742 linked to smoking or drinking?

The variant was identified in a genome-wide study examining smoking and alcohol use phenotypes across 3.4 million participants, but the specific behavioral association and its direction of effect for this individual variant are not detailed in the currently available study text.