Abstract
Background/AimBoth genetics and environment play a role in the development of asthma and wheeze. However, epidemiological studies have not assessed the extent to which genetics modifies risks associated with indoor environmental exposures such as from phthalate exposure. We examined how children’s polygenic risk score (GRS) for asthma modifies the association between early life phthalate exposure and recurrent wheeze.MethodsWe designed a case-cohort study within the CHILD cohort study, a population-based birth cohort, using a random sample of 450 children and adding all children with any recurrent wheeze between 2 to 5 years. House dust samples collected at 3 months of age were analyzed for 6 phthalates. Children were assigned a GRS for asthma computed using multiple genetic variants for childhood asthma identified by Pividori et al (2019). Logistic regression was used to assess the association between phthalate exposure and recurrent wheeze between 2 to 5 years within GRS tertiles. Interaction was examined between phthalate exposure and GRS.Results A stronger effect was observed between DEHP and DiBP exposure and recurrent wheeze risk among children in the lowest GRS tertile compared to the highest tertile. A six-fold increased risk (OR=6.07, 95% CI:2.35-15) and two-fold increased risk (OR=2.55, 95% CI:1.13-5.74) of recurrent wheeze was observed in the second quartile of DEHP and DIBP exposure, respectively, among children in the lowest GRS tertile compared to a two-fold increased risk (OR=2.24, 95% CI:1.19-4.22) and 1.48 times increased risk (95% CI:0.79-2.74) for DEHP and DIBP, respectively, among children in the highest GRS. A significant interaction (p < 0.05) was observed between DEHP, DIBP, and DEP exposure and GRS.ConclusionsPreliminary results suggest that early life phthalate exposure poses a greater risk of developing recurrent wheeze among children with lower genetic risk compared to those with higher genetic risk.
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