Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children

Abstract

To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions ( ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests. Multiple associations were observed for ADAM33: rs2280090 was associated with reduced MEF240% (i.e., the ratio of Mean Expiratory Flow after 240s of hypertonic saline inhalation with respect to the age- and ancestry-matched reference value) and with an increased risk of allergic bronchitis (p = 1.77*10 ⁻⁴ and p = 7.94*10 ⁻⁴, respectively); rs3918396 was associated with wheezing and eczema comorbidity (p = 3.41*10 ⁻⁴). IL4 rs2243250 was associated with increased FEV240 (Forced Expiratory Flow Volume after 240s of hypertonic saline inhalation; p = 4.81*10 ⁻⁴) and CD14 rs2569190 was associated with asthma diagnosis (p = 1.36*10 ⁻³). ADAM33 and IL4 appeared to play a role in the processes linked to allergic airway inflammation and lung function. Due to its association with wheezing and eczema comorbidity, ADAM33 may also be involved in the atopic march.