Rare variants in PLA2G7 are associated with the age of onset and disease burden of asthma

Abstract

Abstract Understanding of the contributions of rare genetic variants in asthma is limited. In this study, we investigated this contribution in 121 asthma-associated genes to the age of onset and disease burden using targeted next-generation sequencing in 576 cases of asthma. The Sequence Kernel Association Test (SKAT) was used for cumulative rare variant association analysis, with asthma onset as the outcome. The median age of onset was 12 years (IQR 5–21) and 65% of the patients developed asthma before age 16. Ninety-two genes with ≥ 10 rare variants (MAF ≤ 1%) were available for the SKAT analysis. We found a cumulative effect (p = 0.015, uncorrected for multiple testing) of rare variants of PLA2G7 (phospholipase A2, group VII) and asthma onset. PLA2G7 rare variant carriers showed higher levels of FeNO than PLA2G7 non-carriers (18 ppb (IQR 14–30) vs. 13 ppb (IQR 8–21), p = 0.013). Furthermore, FEV1 was reduced in the PLA2G7 carriers compared to the non-carriers (87.6% (12.3) vs. 96.0% (13.6), p = 0.018). In conclusion, we found an association between the PLA2G2 locus and the age of onset in a population of Norwegian patients with asthma. Furthermore, increased FeNO and reduced FEV1 were observed among the PLA2G7 carriers.