Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studies in 2653 male asthma cases, 2566 female asthma cases and 3830 non-asthma controls from European American, African American, African Caribbean and Latino populations. Association tests were conducted in each study sample, and the results were combined in ancestry-specific and cross-ancestry meta-analyses. Six sex-specific asthma risk loci had P-values < 1 × 10(-6), of which two were male specific and four were female specific; all were ancestry specific. The most significant sex-specific association in European Americans was at the interferon regulatory factor 1 (IRF1) locus on 5q31.1. We also identify a Latino female-specific association in RAP1GAP2. Both of these loci included single-nucleotide polymorphisms that are known expression quantitative trait loci and have been associated with asthma in independent studies. The IRF1 locus is a strong candidate region for male-specific asthma susceptibility due to the association and validation we demonstrate here, the known role of IRF1 in asthma-relevant immune pathways and prior reports of sex-specific differences in interferon responses.

Asthma and allergic rhinitis were analyzed in a random sample of school children (n=6174) residing in Ciudad Juarez, Chihuahua, Mexico. The International Study of Asthma and Allergies in Childhood methodology was applied through a standardized questionnaire. The sample was obtained with a bietapic design. Cumulative prevalence of asthma and wheezing was 6.8% (95% CI 6.2, 7.4) and 20% (95% of CI 19.7, 21.8) respectively; the prevalence of rhinitis was 5.0% (95% CI 4.5, 5.6). Family history of asthma odds ratio (OR) 2.33 (95% CI 1.78-3.05), respiratory infection after birth (OR) 3.44 (95% CI 2.76-4.29), and exposure to environmental tobacco (OR) 1.35 (95% CI 1.06-1.68) were the strongest risk factors for asthma and allergic rhinitis. The multifactorial etiology of asthma and allergic rhinitis was confirmed, as well as the importance of early exposure to environmental factors.

Background Childhood obesity continues to be a global health problem. Previous research suggests that linear growth retardation or stunting during early childhood increases the risk of obesity, but others have reported that rapid linear growth poses a greater concern than early nutritional status. Objective The objective of this study was to determine if growth trajectories are associated with body composition at age 8–10 y. Methods Study participants consisted of 255 girls and 281 boys who participated in a follow-up of the Prenatal Omega-3 Fatty Acid Supplementation and Child Growth and Development (POSGRAD) Study. Sex-specific latent height class (LHC) trajectories were derived from 11 measures of height from birth to 5 y of age and used to calculate 3 distinct growth classes for boys (low, intermediate, and high) and 2 distinct classes for girls (low and high). Body composition at age 8–10 y was estimated using bioelectrical impedance analysis. Multivariable linear regression analysis was used to determine the relationship between growth trajectory classes and fat mass (FM) and fat-free mass (FFM) in late childhood, controlling for confounding factors. Results In girls, there were no significant associations between LHC and FM or FFM. In boys, relative to the intermediate LHC, the low LHC had higher FM (β = 0.69 kg; 95% CI: 0.26−1.11 kg) and the high LHC had lower FM (β = −0.40 kg; 95% CI: −0.76 to −0.05 kg). Boys in the low LHC had significantly less FFM (β = −0.69 kg; 95% CI: −1.11 to −0.26 kg), and boys in the high LHC had more FFM (β = 0.40 kg; 95% CI: 0.05−0.76 kg) compared with the intermediate LHC. Conclusion Gain in height among boys, but not girls, in early childhood was associated with lower adiposity in late childhood compared with children with a slower rate of growth. Clinical trial registration number: NCT00646360

Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Objective: Asthmatic children who develop obesity through adolescence have poorer disease outcomes compared to those that do not. We aimed to characterize the biology of childhood asthma complicated by adult obesity. Methods: Gene expression networks are powerful statistical tools for characterizing human disease that leverage the putative co-regulatory relationships of genes to infer relevant biological pathways. We performed weighted gene co-expression network analysis (WGCNA) of gene expression data in whole blood from 514 adult asthmatic subjects. We then performed module preservation and association replication analyses in 418 subjects from two independent asthma cohorts (one pediatric and one adult). Results: We identified a multivariate model in which three gene co-expression network modules were associated with incident obesity in the discovery cohort (each P < 0.05). Two module memberships were enriched for genes in pathways related to platelets, integrins, extracellular matrix, smooth muscle, NF-κB signaling, and Hedgehog signaling. The network structures of each of the obese asthma modules were significantly preserved in both replication cohorts (permutation P = 9.999E-05). The corresponding module gene sets were significantly enriched for differential expression in subjects who were obese in both replication cohorts (each P < 0.05). Conclusions: Our gene co-expression network profiles thus implicate multiple interrelated pathways in the biology of an important endotype of obese asthma.