Expressive

rs1079572 (WWOX): Lung Capacity Variant

Key takeaways

  • rs1079572, near WWOX, is a genome-wide significant hit for forced vital capacity in over 52,000 people
  • WWOX transcripts were confirmed in human lung tissue, supporting a biological role in lung function
  • This variant reduces WWOX expression in the brain amygdala and raises expression of a nearby gene in testis
  • Evidence is from European-ancestry populations; replication in non-European groups was limited
  • No per-SNP effect size for this variant was reported in the available study text

Key takeaways

  • rs1079572, near WWOX (WW domain-containing oxidoreductase), was identified as a genome-wide significant locus for forced vital capacity (FVC), a measure of total exhaled lung volume used to detect restrictive lung disease
  • The finding came from a meta-analysis of over 52,000 Europeans, replicated in nearly 33,000 more - one of the larger lung-function genomic studies at the time
  • Transcripts for this gene were confirmed in human lung tissue, airway smooth muscle cells, and bronchial epithelial cells, supporting a plausible biological role
  • The alternate allele at this locus reduces WWOX expression in the brain amygdala and increases expression of a neighboring transcript in testis
  • Replication in non-European populations was limited, and no per-SNP effect size was reported in the available study text

What the research says A two-stage GWAS meta-analysis identified rs1079572, near WWOX, as one of six novel loci reaching genome-wide significance (P < 5 × 10^-8) for FVC in 52,253 European-ancestry individuals, with replication across an independent 32,917 Europeans. Transcripts for this gene were detected in human lung tissue, airway smooth muscle cells, bronchial epithelial cells, and peripheral blood mononuclear cells, lending biological plausibility to the association. GTEx v11 data (953 donors, FDR < 0.05) additionally show that the alternate allele at this locus associates with reduced expression in the brain amygdala and increased expression of the neighboring transcript ENSG00000261540 in testis GTEx Portal.

Reported associations

  • Forced vital capacity (FVC): genome-wide significant association (P < 5 × 10^-8) in 52,253 discovery-stage Europeans across 26 cohorts, replicated in 32,917 additional Europeans across 9 independent cohorts; FVC is used to diagnose and monitor restrictive lung disorders such as idiopathic pulmonary fibrosis
  • WWOX expression in the brain amygdala: the alternate allele is associated with reduced transcript levels in this brain region (GTEx slope −0.22, FDR < 0.05, 953 donors) GTEx Portal
  • ENSG00000261540 expression in testis: the alternate allele is associated with increased expression of this neighboring transcript in testicular tissue (GTEx slope +0.34, FDR < 0.05, 953 donors) GTEx Portal

Evidence quality The FVC signal rests on a large two-stage design: 52,253 individuals across 26 discovery cohorts followed by replication in 32,917 Europeans across 9 independent cohorts, achieving genome-wide significance. Expression QTL analyses were also performed in 762 whole-blood samples, and WWOX mRNA was confirmed in lung tissue, supporting biological plausibility. No per-SNP beta coefficient or percentage of variance explained is reported for this specific locus in the available text, limiting precision of the effect estimate. Multi-ethnic follow-up was conducted for the broader set of loci (African Americans n = 6,070; Koreans n = 8,074; Chinese n = 563; Hispanics n = 849), though results specific to rs1079572 in non-European populations are not detailed in the available excerpt. GTEx eQTL evidence (953 donors, FDR < 0.05) reflects tissue-specific regulatory effects and should be read as mechanism-level observations, not clinical outcomes GTEx Portal. No conflicting evidence for this locus appears in the provided studies.

Tissue-specific expression effects

  • WWOX: reduced expression in the brain amygdala - the alternate allele is associated with lower transcript levels in this brain region GTEx Portal
  • ENSG00000261540: increased expression in testis - the alternate allele is associated with higher levels of this neighboring transcript in testicular tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs1079572?

rs1079572 is a genetic variant located near the WWOX gene that was identified as significantly associated with forced vital capacity in a large genome-wide association study of over 52,000 Europeans.

What does the WWOX gene do?

WWOX (WW domain-containing oxidoreductase) is a gene whose transcripts have been detected in human lung tissue, airway smooth muscle cells, and bronchial epithelial cells. Its precise role in lung function remains under study.

Is rs1079572 linked to lung disease?

This variant was significantly associated with forced vital capacity, a lung volume measure used to detect restrictive conditions such as idiopathic pulmonary fibrosis. The study identified the statistical association but did not establish a direct causal link to a specific disease.

Does rs1079572 affect the brain?

GTEx data show the alternate allele of rs1079572 is associated with reduced WWOX expression in the brain amygdala. This is a gene-expression finding and does not establish a connection to any brain disorder or cognitive trait.

How large was the study that identified this variant?

The discovery included 52,253 individuals of European ancestry across 26 studies, with replication in 32,917 additional Europeans across 9 independent cohorts, making it one of the larger lung-function GWAS analyses at the time of publication.