We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 cases, 118,538 controls) from ethnically-diverse populations. We identified five new asthma loci, uncovered two additional novel associations at two known asthma loci, established asthma associations at two loci implicated previously in comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. Enrichment of asthma risk loci in enhancer marks, especially in immune cells, suggests a major role of these loci in the regulation of immune-related mechanisms.

Exposures to ambient air pollutants have been associated with adverse birth outcomes. We investigated the effects of air pollutants on birth weight mediated by reduced fetal growth among term infants who were born in California during 1975–1987 and who participated in the Children’s Health Study. Birth certificates provided maternal reproductive history and residence location at birth. Sociodemographic factors and maternal smoking during pregnancy were collected by questionnaire. Monthly average air pollutant levels were interpolated from monitors to the ZIP code of maternal residence at childbirth. Results from linear mixed-effects regression models showed that a 12-ppb increase in 24-hr ozone averaged over the entire pregnancy was associated with 47.2 g lower birth weight [95% confidence interval (CI), 27.4–67.0 g], and this association was most robust for exposures during the second and third trimesters. A 1.4-ppm difference in first-trimester carbon monoxide exposure was associated with 21.7 g lower birth weight (95% CI, 1.1–42.3 g) and 20% increased risk of intrauterine growth retardation (95% CI, 1.0–1.4). First-trimester CO and third-trimester O3 exposures were associated with 20% increased risk of intrauterine growth retardation. A 20-μg/m3 difference in levels of particulate matter ≤ 10 μm in aerodynamic diameter (PM10) during the third trimester was associated with a 21.7-g lower birth weight (95% CI, 1.1–42.2 g), but this association was reduced and not significant after adjusting for O3. In summary, O3 exposure during the second and third trimesters and CO exposure during the first trimester were associated with reduced birth weight.

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There is consistent evidence that living near traffic sources is associated with asthma occurrence and exacerbations. Future studies have the opportunity to improve exposure estimates by measuring traffic-related pollutants near homes and schools and including time/activity patterns in prediction models. Further research is also warranted to investigate the differential impact of traffic by genetic and other susceptibility factors and to identify specific pollutants that underlie the adverse effect of traffic on asthma.