Revisiting and dissecting the maternal effect on childhood asthma

The project has located a gene that gives a larger risk of asthma in the child when it is inherited from the mother than when it is inherited from the father. This can partly explain why asthma is more common when the mother has asthma than when the father has it.

It is well established that childhood asthma is more common when the mother has asthma than when the father has it. Although this has been reproduced by many researchers, none of them have come up with a good explanation for the effect. At present there is no efficient primary prevention of childhood asthma, due to lack of etiological Insight. We aim to discover the biology behind the maternal effect using data from a large pregnancy cohort, the Norwegian Mother, Father, and Child Cohort Study (MoBa), and from nation-wide registries. We are organising the project in three themes; Theme A: Quantitative genetics based on familiy designs, Theme B: Molecular genetics and Theme C: Environmental factors and gene-environment interactions. We will use the mandatory Norwegian Prescription Database (NorPD) to define childhood asthma based on certain dispensed medications. For Theme A we will organise the population registry into informative pedigrees and link these to the NorPD in order to estimate the maternal genetic variance. This will also be estimated from MoBa pedigrees. In Theme B, we will use genome-wide genotyping data to estimate maternal genetic effects, including parent-of-origin effects and X-linked inheritance. In addition, we will measure telomere length and sequence the mitochondrial genome at birth for children who later do or do not develop asthma. In Theme C we will study whether the maternal effect is due to maternal disease activity during pregnancy. We will also calculate polygenic scores and use them both as instrumental variables for parental exposures, but also for dividing the sample into high and low risk strata, to discover gene-environment interactions. We believe, due to the available data resources and the cross-disciplinary competence in our research group, that we can achieve new insights that will help prevent the occurrence of childhood asthma.