Parent-of-Origin Effects in Childhood Asthma at Seven Years of Age

Abstract

Childhood asthma is more common among children whose mothers have asthma than among those whose fathers have asthma. The reasons for this are unknown, and we hypothesize that genomic imprinting may partly explain this observation. Our aim is to assess parent-of-origin (PoO) effects on childhood asthma by analyzing SNP array genotype data from a large population-based cohort. To estimate PoO effects in parent-reported childhood asthma at 7 years of age, we fit a log-linear model implemented in the HAPLIN R package to SNP array genotype data from 915 mother-father-child case triads, 603 mother-child case dyads, and 113 father-child case dyads participating in the Norwegian Mother, Father, and Child Cohort Study (MoBa). We found that alleles at two SNPs-rs3003214 and rs3003211-near the adenylosuccinate synthase 2 gene (ADSS2 on chromosome 1q44) showed significant PoO effects at a false positive rate ≤ 0.05. The ratio of the effect of the maternally and paternally inherited G-allele at rs3003214 was 1.68 (95% CI: 1.41-2.03, p value = 1.13E-08). Our results suggest PoO effects at the ADSS2 gene, particularly the maternally inherited G-allele at rs3003214, may contribute to the maternal effect in childhood asthma.

Keywords: GWAS; Haplin; Norwegian Mother, Father, and Child Cohort Study (MoBa); childhood asthma; genetics; parent‐of‐origin.