O-111 A Genome-wide Association Study Of Variants Associated With Genetic Susceptibility To Severe Bronchiolitis

Abstract

Background and aims Respiratory syncytial virus (RSV) bronchiolitis is the primary cause of hospital admission among children under two years and it is considered to be a risk factor for developing asthma later in life. Although some genetic variants associated with bronchiolitis have been identified by candidate gene studies, the genetic background of the disease is not well understood. Here, we aimed to identify genetic polymorphisms conferring susceptibility to severe bronchiolitis and subsequent asthma. Methods Case-control discovery cohorts with 94 cases of severe bronchiolitis and 94 controls collected in Finland and Sweden were genotyped with Illumina HumanOmniExpress BeadChip containing 700.000 SNPs. Replication population of 130 cases and 250 controls collected in Finland is being genotyped with HumanCoreExome BeadChip containing 500.000 SNPs. Respiratory outcomes of all the cohorts have been followed-up to 5–30 years of age. Association signals are further analysed in appropriate functional studies. Results In the discovery data set, several signals indicating association with bronchiolitis were identified. As an example, SNPs within ADAR (adenosine deaminase, RNA-specific) and KLRK1 (killer cell lectin-like receptor subfamily K, member 1) genes involved e.g. in immune responses showed suggestive associations (p-value ≤10 –4 ). Some of the SNPs previously reported to be associated with bronchiolitis showed weaker signals. Conclusions We found suggestive association signals for several SNPs. Associations observed both in the discovery population and in the replication cohort are regarded as plausible candidates for further studies. The most promising candidate genes will be analysed in functional studies to verify their potential role in bronchiolitis.