rs1105491 (SFRP2-DCHS2): Lung Function Variant

Key takeaways

• Identified in the largest multi-ancestry lung function genome-wide association study to date, covering 588,452 participants across five ancestry groups
• Among 1,020 independent genetic signals linked to breathing capacity measures including FEV1, FVC, and peak expiratory flow
• Lung function variants from this study collectively predict COPD risk across African, East Asian, Hispanic, South Asian, and European populations
• GTEx data shows this variant increases TLR2 expression in skin and fibroblast tissue, connecting this locus to innate immune signaling
• No lifestyle interventions have been specifically studied for this individual variant

What the research says

A multi-ancestry genome-wide association meta-analysis enrolling 588,452 individuals identified 1,020 independent signals for spirometric lung function, implicating 559 candidate genes through a systematic variant-to-gene mapping framework that integrated eight lines of functional evidence. Lung function traits examined included forced expiratory volume in 1 second (FEV1 - air exhaled in one second during a forced breath), forced vital capacity (FVC - total air forcibly exhaled), the FEV1/FVC ratio (a standard index of airway obstruction), and peak expiratory flow rate (PEF - the highest speed of exhalation). When aggregated into a genetic risk score, the identified variants showed strong association with chronic obstructive pulmonary disease (COPD) across African, American/Hispanic, East Asian, South Asian, and European ancestry groups.

Reported associations

• Lung function (FEV1, FVC, FEV1/FVC, PEF): rs1105491 near the SFRP2-DCHS2 locus was identified among 1,020 independent signals in a multi-ancestry GWAS of four spirometric traits (n = 588,452); no variant-specific effect size was reported in the provided text excerpt.
• COPD risk: In the same study, genetic risk scores built from lung function signals - including signals from this locus - associated with COPD case-control status across multiple ancestry groups, indicating a contribution to the polygenic architecture of obstructive airway disease.

Evidence quality

The lung function association derives from a large, well-powered multi-ancestry GWAS (n = 588,452), the largest of its kind at time of publication. Genomic inflation was well-controlled across all four traits (λ = 1.025, 1.022, 0.984, and 0.996 for FEV1, FVC, FEV1/FVC, and PEF, respectively). A systematic variant-to-gene mapping framework requiring support from at least two out of eight criteria was applied to prioritize likely causal genes across the 1,020 signals. No variant-specific p-value, effect size, or independent replication data for rs1105491 were provided in the available text excerpt. These associations should be regarded as discovery-stage findings pending functional follow-up.

Tissue-specific expression effects

• TLR2: The alternative allele is associated with increased expression in cultured fibroblasts, sun-unexposed suprapubic skin, and sun-exposed lower-leg skin - three directionally consistent signals pointing to upregulated expression in connective and skin tissue GTEx Portal.
• RNF175: The alternative allele associates with increased expression in cultured fibroblasts and sun-unexposed skin, but decreased expression in frontal cortex brain tissue - directional effects that diverge by tissue type GTEx Portal.
• ENSG00000280241: The alternative allele associates with decreased expression in whole blood and increased expression in tibial nerve - opposing directional effects across these two tissue types GTEx Portal.

Lifestyle considerations

No lifestyle considerations on file for this variant.