Expressive

rs11153056 (PDSS2): Lung Function & Smoke Exposure

Key takeaways

  • The alternate allele reduces PDSS2 expression in 8 tissue types, including esophagus, stomach, and tibial artery
  • A genome-wide study flagged this variant as a possible modifier of secondhand smoke's effect on lung airflow (FEV1)
  • The gene-expression evidence is robust across tissues; the lung-function interaction finding is preliminary
  • Enriched pathways in the lung-function analysis include apoptosis, p38 MAPK, and TNF signaling

Key takeaways

  • The alternate allele reduces PDSS2 expression across 8 tissue types, including esophagus, stomach, and tibial artery
  • A genome-wide study flagged this variant as a possible modifier of how secondhand smoke affects lung airflow (FEV1)
  • The gene-expression evidence is robust across tissues; the lung-function interaction finding is preliminary
  • Enriched pathways in the lung-function analysis include apoptosis, p38 MAPK, and TNF signaling

What the research says A genome-wide interaction study in 10,817 Dutch adults examined whether common genetic variants modify the effect of secondhand smoke (environmental tobacco smoke, or ETS) on forced expiratory volume in one second (FEV1 - the volume of air forcibly exhaled in one second, a standard measure of airway function); 45 candidate SNP-by-ETS interactions reached p<10^-4 in that cohort, and 2 were replicated at nominal significance (p<0.05) in at least one of two additional cohorts totaling approximately 2,432 subjects. Separately, GTEx v11 data (953 donors) show that the alternate allele of rs11153056 consistently reduces PDSS2 expression across 8 tissue types with slopes ranging from −0.11 to −0.16, all at FDR<0.05 (false discovery rate - a statistical threshold controlling the proportion of false positives among significant results) GTEx Portal.

Reported associations

  • Lung function (FEV1) - secondhand smoke interaction: rs11153056 in the PDSS2 region was among 45 variants identified in a genome-wide interaction study as candidates for modifying the effect of ETS on FEV1 (identification cohort n=10,817); biological pathways enriched in the analysis included apoptosis, p38 MAPK, and TNF signaling.
  • PDSS2 expression - esophagus mucosa: The alternate allele is associated with reduced expression (slope −0.16, p=6.1×10^-8) GTEx Portal.
  • PDSS2 expression - esophagus muscularis: The alternate allele is associated with reduced expression (slope −0.13, p=5.7×10^-8) GTEx Portal.
  • PDSS2 expression - cultured fibroblasts: The alternate allele is associated with reduced expression (slope −0.15, p=1.6×10^-7) GTEx Portal.
  • PDSS2 expression - tibial artery: The alternate allele is associated with reduced expression (slope −0.14, p=1.9×10^-7) GTEx Portal.
  • PDSS2 expression - colon transverse: The alternate allele is associated with reduced expression (slope −0.11, p=2.5×10^-7) GTEx Portal.
  • PDSS2 expression - adrenal gland: The alternate allele is associated with reduced expression (slope −0.13, p=2.8×10^-6) GTEx Portal.
  • PDSS2 expression - stomach: The alternate allele is associated with reduced expression (slope −0.14, p=1.8×10^-5) GTEx Portal.
  • PDSS2 expression - EBV-transformed lymphocytes: The alternate allele is associated with reduced expression (slope −0.15, p=1.7×10^-5) GTEx Portal.

Evidence quality The lung-function/ETS interaction evidence comes from a single genome-wide interaction study (identification cohort: n=10,817; replication cohorts: SAPALDIA n=1,276, Rotterdam Study n=1,156). The replication criterion was nominal significance (p<0.05) in at least one cohort - a lenient threshold well below conventional genome-wide significance (p<5×10^-8); only 2 of 45 candidate variants cleared this bar, and the available study text does not confirm whether rs11153056 was among them. This lung-function association must therefore be regarded as preliminary. By contrast, the eQTL (expression quantitative trait locus - a genetic variant with a statistically supported effect on nearby gene expression levels) evidence from GTEx is more robust: eight independent tissue types all show consistent negative direction, p-values as low as 1.6×10^-7, and FDR-corrected significance throughout, derived from 953 donors in GTEx v11 GTEx Portal. eQTL associations reflect a molecular mechanism and do not by themselves establish clinical outcomes.

Tissue-specific expression effects

  • PDSS2: The alternate allele is linked to reduced expression in 8 tissue types - esophagus mucosa, esophagus muscularis, cultured fibroblasts, EBV-transformed lymphocytes, stomach, tibial artery, adrenal gland, and colon transverse - with a consistent negative direction at FDR<0.05 across all sites GTEx Portal.

Lifestyle considerations

  • Secondhand smoke (lifestyle, exclude, low): A genome-wide interaction study identified this variant as a candidate modifier of secondhand smoke's effect on lung airflow, though the specific replication status of this variant is uncertain and the evidence is preliminary.

Frequently asked questions

What is rs11153056?

rs11153056 is a single nucleotide polymorphism (SNP) - a common one-letter variation in the DNA sequence - located in the PDSS2 gene. The alternate allele is consistently associated with reduced PDSS2 expression across multiple tissue types.

Is rs11153056 linked to lung disease?

A genome-wide interaction study identified rs11153056 as a candidate modifier of how secondhand smoke affects FEV1, a standard measure of lung airflow. The evidence is preliminary, and the specific replication status of this variant has not been definitively established.

Which tissues does rs11153056 affect PDSS2 expression in?

Based on GTEx data from 953 donors, the alternate allele is associated with reduced PDSS2 expression in esophagus mucosa, esophagus muscularis, cultured fibroblasts, EBV-transformed lymphocytes, stomach, tibial artery, adrenal gland, and colon transverse - all at FDR<0.05.

How does secondhand smoke relate to rs11153056?

A genome-wide study in over 10,000 adults examined whether genetic variants modify the effect of secondhand smoke on lung function. rs11153056 was among 45 candidate variants identified in the discovery phase, though only 2 of those 45 were replicated at even nominal significance.

How strong is the evidence for rs11153056?

The tissue expression evidence is robust, showing consistent effects across 8 tissue types in a large reference dataset at FDR-corrected significance. The lung-function interaction evidence is weaker, based on a single study using a lenient replication threshold without genome-wide significance confirmation.