Early life factors and genetic interactions in allergic rhinitis: a genome-wide study

Early life factors play an important role in the development and progression of allergic rhinitis (AR), but their relationship and underlying genetic mechanisms still remains unclear.

Using cross-sectional data from the UK Biobank (UKB) and West China Hospital (WCH), we assessed the associations between nine early life factors-birth weight, body size and height at age 10, multiple births, maternal smoking around birth, breastfeeding, long-term/recurrent antibiotic usage as a child or teenager (LTRAU), cesarean delivery, and maternal age-and the development of AR through multivariable logistic regression models. We also conducted a genome-wide gene-environment interaction study (GWGEIS) to explore the correlation between polygenic risk scores (PRS) derived from GWGEIS and AR risk.

In both UKB and WCH cohorts, LTRAU (UKB cohort: OR = 1.49, P < 0.001; WCH cohort: OR = 2.18, P < 0.001), and born by cesarean delivery (UKB cohort: OR = 1.26, P = 0.0014; WCH cohort: OR = 1.47, P = 0.008) were identified as independent risk factors for AR. Notably, the association between cesarean delivery and an increased risk of AR was confined to female offspring who developed AR before the age of 16. In contrast, the detrimental effects of LTRAU remained significant in offspring who developed AR after the age of 16. Additionally, GWGEIS identified an interaction between the ATE1 gene and LTRAU (rs4752620, P = 2.51E-8, β = -0.30). Furthermore, the PRS derived from GWGEIS results was significantly associated with the risk of AR (OR = 1.06, P = 0.038).

These findings enhance our understanding of how early life factors, particularly LTRAU, and genetic factors synergistically affect AR risk, offering valuable insights for prevention and treatment strategies.