The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Measuring Satisfaction with Mammography Results Reporting

OBJECTIVE: To assess factors associated with patient satisfaction with communication of mammography results and their understanding and ability to recall these results. DESIGN: Cross-sectional telephone survey. SETTING: Academic breast imaging center. PATIENTS: Two hundred ninety-eight patients who had either a screening or diagnostic mammogram. MEASUREMENTS AND MAIN RESULTS: Survey items assessed waiting time for results, anxiety about results, satisfaction with several components of results reporting, and patients' understanding of results and recommendations. Women undergoing screening exams were more likely to be dissatisfied with the way the results were communicated than those who underwent diagnostic exams and received immediate results (20% vs 11%, P = .05). For these screening patients, waiting for more than two weeks for notification of results, difficulty getting in touch with someone to answer questions, low ratings of how clearly results were explained, and considerable or extreme anxiety about the results were all independently associated with dissatisfaction with the way the results were reported, while age and actual exam result were not. CONCLUSIONS: Patients undergoing screening mammograms were more likely to be dissatisfied with the way the results were communicated than were those who underwent diagnostic mammograms. Interventions to reduce the wait time for results, reduce patients' anxiety, and improve the clarity with which the results and recommendations are given may help improve overall satisfaction with mammography result reporting

Heritability estimates on Hodgkin’s lymphoma: a genomic- versus population-based approach

Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) influencing the risk of Hodgkin's lymphoma (HL) and demonstrated the association of common genetic variation for this type of cancer. Such evidence for inherited genetic risk is also provided by the family history and the very high concordance between monozygotic twins. However, little is known about the genetic and environmental contributions. A common measure for describing the phenotypic variation due to genetics is the heritability. Using GWAS data on 906 HL cases by considering all typed SNPs simultaneously, we have calculated that the common variance explained by SNPs accounts for >35% of the total variation on the liability scale in HL (95% confidence interval 6-62%). These findings are consistent with similar heritability estimates of ∼0.40 (95% confidence interval 0.17-0.58) based on Swedish population data. Our estimates support the underlying polygenic basis for susceptibility to HL, and show that heritability based on the population data is somehow larger than heritability based on the genomic data because of the possibility of some missing heritability in the GWAS data. Besides that there is still major evidence for multiple loci causing HL on chromosomes other than chromosome 6 that need to be detected. Because of limited findings in prior GWASs, it seems worth checking for more loci causing susceptibility to HL.European Journal of Human Genetics advance online publication, 17 September 2014; doi:10.1038/ejhg.2014.184

Ambient air pollution and low birthweight: a European cohort study (ESCAPE)

Background Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight. Methods We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and between 2.5 mu m and 10 mu m during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2.5 absorbance and concentrations of nitrogen dioxide (NO 2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models. Findings A 5 mu g/m(3) increase in concentration of PM2.5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1.18, 95% CI 1.06-1.33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2.5 limit of 25 mu g/m(3) (OR for 5 mu g/m(3) increase in participants exposed to concentrations of less than 20 mu g/m(3) 1.41, 95% CI 1.20-1.65). PM10 (OR for 10 mu g/m(3) increase 1.16, 95% CI 1.00-1.35), NO2 (OR for 10 mu g/m(3) increase 1.09, 1.00-1.19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1.06, 1.01-1.11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2.5 concentration to 10 mu g/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term. Interpretation Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced

A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)

To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 x 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 x 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 x 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 x 10(-50)). These data provide new insight into the pathogenesis of cHL

Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility (vol 8, 1892, 2017)

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.status: publishe