Genome-wide interaction study on occupational hazards and asthma, the European Community Respiratory Health Survey (ECRHS)
本研究基于欧洲人群队列，首次在全基因组水平探索职业暴露（高分子量物质和乳胶）与哮喘的基因-环境交互作用，发现少数有提示意义的SNP位点，但结果依赖于暴露定义和分析策略。
Objectives Very few studies have addressed gene-environment (GxE) interactions in asthma at the genome-wide level and none in the context of occupational hazards. Our objective was to detect GxE interactions for asthma and job exposure in a population-based cohort. Methods Occupational exposures for 2205 adults from the ECRHS were assessed through job histories, an asthma-specific JEM and expert assessment. We performed a genome-wide interaction analysis for asthma as a whole and adult onset asthma by using 582 892 single nucleotide polymorphisms (SNP) and work exposure to high-molecular weight agents (HMW) and latex. Two analytical strategies were used to detect GxE interactions: 1) a global genome-wide analysis and 2) a two-stage approach. Results In the global analysis, a single SNP with marginal genome-wide significance (p<1.E-07) emerged to interact with latex for adult onset asthma. In the two-stage approach, SNPs associated with exposure (p<1.E-05) at the first step were then tested for association with outcomes at the second step. In this approach, two SNPs were detected to interact with HMW and four SNPs with latex for adult onset asthma (p<0.05). These SNPs were not among the top 30 SNPs in the global analysis. Conclusions We found very few clues on GxE interactions. Results depended not only on exposure and outcome definitions, with slightly lower p-values for the more specific definitions (adult onset, latex) but also on the analytical strategy followed. Replication of these findings will be presented using two additional studies (EGEA and Sapaldia).