Novel susceptibility loci link occupational exposure to vapors, dusts, gases and fumes to lung function level in the lifelines cohort study

Rationale Hypothesis free genome wide association (GWA) studies have revealed genetic loci that are associated with lung function levels and risk for Chronic Obstructive Pulmonary Disease (COPD). The next step will be to perform hypothesis free genome-wide interaction studies (GWIS) to identify genetic loci that modify the detrimental effects of occupational exposures. These findings may contribute to find and understand biological pathways leading to disease, as well as to detect susceptible subgroups within the general population. To date no studies have investigated genetic interactions between common occupational exposures and level of lung function in the general population. Methods We performed GWIS analysis to identify novel loci that modify the association between occupational exposure to vapors, gases, dust and fumes (VGDF) and lung function level (FEV1, FEV1/FVC) in 12,400 subjects from the LifeLines cohort study. The ALOHA+ Job Exposure Matrix was used to estimate occupational exposure to VGDF for each subject as no, low, and high exposure (0/1/2). Interactions of low and high VGDF exposure with 227,981 genotyped SNPs (IlluminaCytoSNP-12 arrays) on lung function levels were tested in an additive genetic model adjusted for sex, age, height and ever smoking (no/yes), using linear regression in the software package PLINK. Results For the level of FEV1, we identified 9 SNPs with p-values for interaction with VGDF (all with high exposure) at p