Food allergy (FA) affects 2–10% of U.S. children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk, and egg) in 2,759 U.S. participants (1,315 children; 1,444 parents) from the Chicago Food Allergy Study; and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (p=5.5×10−8) and rs9275596 (p=6.8×10−10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (p<5×10−8); and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region likely poses significant genetic risk for PA.

We found a strong joint effect of prematurity and chorioamnionitis on early childhood wheezing. This effect was stronger in African American subjects.

Background The relationship between the prenatal environment, maternal-fetal interaction, and allergic disease in the offspring remains understudied. Objective We sought to determine whether gestational diabetes modifies the risk of early childhood atopic manifestations including atopic dermatitis and allergen sensitization. Methods This study includes 680 children from the Boston Birth Cohort. Mother-child dyads were recruited at birth and followed prospectively to a mean age of 3.2±2.3 years with study visits aligned with the pediatric primary care schedule. The primary outcomes were physician diagnosed atopic dermatitis on standardized medical record abstraction and allergen sensitization based on Immunocap to 7 common foods and 5 common aeroallergens (sIgE≥0.10 kUA/L, Phadia). Gestational diabetes was determined by standardized medical record review. Logistic regression analysis, stratified by term/preterm status, evaluated the association of gestational diabetes with atopic dermatitis and allergen sensitization respectively, controlling for maternal pre-pregnancy BMI, fetal growth, and pertinent covariates. Results Of the 680 children, 488 were term and 192 were preterm (<37 weeks gestation). Overall, 4.9% of the mothers developed gestational diabetes. Among the 680 children, 34.4% developed atopic dermatitis and 51% developed allergen sensitization. In term births, gestational diabetes was significantly associated with atopic dermatitis (OR, 95%CI=7.2, 1.5-34.5) and allergen sensitization (OR, 95%CI=5.7, 1.2-28.0). Adjusting for fetal growth had little effect. The association with sensitization was driven primarily by food sensitization (OR, 95%CI=8.3, 1.6-43.3). The above associations were not observed in preterm births. Conclusions In term births, gestational diabetes increased the risk of atopic dermatitis and early childhood allergen sensitization, independent of maternal pre-pregnancy BMI and fetal growth.