Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis.

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BackgroundTraffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma.ObjectivesWe evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools.MethodsParent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children’s Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO2), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric.ResultsAsthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25–1.82] and near schools (HR 1.45; 95% CI, 1.06–1.98). Ambient NO2 measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18–4.01). In models with both NO2 and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO2 was attenuated (HR 1.37; 95% CI, 0.69–2.71).ConclusionsTraffic-related pollution exposure at school and homes may both contribute to the development of asthma.

To determine the relation between obesity and new-onset asthma among school-age children, the authors examined longitudinal data from 3,792 participants in the Children's Health Study (Southern California) who were asthma-free at enrollment. New cases of physician-diagnosed asthma, height, weight, lung function, and risk factors for asthma were assessed annually at five school visits between 1993 and 1998. Incidence rates were calculated, and proportional hazards regression models were fitted to estimate the adjusted relative risks of new-onset asthma associated with percentile of body mass index (weight (kg)/height (m)(2)) and indicators of overweight (>85th body mass index percentile) and obesity (>95th body mass index percentile). The risk of new-onset asthma was higher among children who were overweight (relative risk (RR) = 1.52, 95% confidence interval (CI): 1.14, 2.03) or obese (RR = 1.60, 95% CI: 1.08, 2.36). Boys had an increased risk associated with being overweight (RR = 2.06, 95% 1.33, 3.18) in comparison with girls (RR = 1.25, 95% CI: 0.83, 1.88). The effect of being overweight was greater in nonallergic children (RR = 1.77, 95% CI: 1.26, 2.49) than in allergic children (RR = 1.16, 95% CI: 0.63, 2.15). The authors conclude that being overweight is associated with an increased risk of new-onset asthma in boys and in nonallergic children.

BackgroundBiologically plausible mechanisms link traffic-related air pollution to metabolic disorders and potentially to obesity. Here we sought to determine whether traffic density and traffic-related air pollution were positively associated with growth in body mass index (BMI = kg/m2) in children aged 5–11 years.MethodsParticipants were drawn from a prospective cohort of children who lived in 13 communities across Southern California (N = 4550). Children were enrolled while attending kindergarten and first grade and followed for 4 years, with height and weight measured annually. Dispersion models were used to estimate exposure to traffic-related air pollution. Multilevel models were used to estimate and test traffic density and traffic pollution related to BMI growth. Data were collected between 2002–2010 and analyzed in 2011–12.ResultsTraffic pollution was positively associated with growth in BMI and was robust to adjustment for many confounders. The effect size in the adjusted model indicated about a 13.6% increase in annual BMI growth when comparing the lowest to the highest tenth percentile of air pollution exposure, which resulted in an increase of nearly 0.4 BMI units on attained BMI at age 10. Traffic density also had a positive association with BMI growth, but this effect was less robust in multivariate models.ConclusionsTraffic pollution was positively associated with growth in BMI in children aged 5–11 years. Traffic pollution may be controlled via emission restrictions; changes in land use that promote jobs-housing balance and use of public transit and hence reduce vehicle miles traveled; promotion of zero emissions vehicles; transit and car-sharing programs; or by limiting high pollution traffic, such as diesel trucks, from residential areas or places where children play outdoors, such as schools and parks. These measures may have beneficial effects in terms of reduced obesity formation in children.