Anorexia nervosa (AN) is a mental illness with high mortality that most commonly afflicts adolescent female individuals. Clinical symptoms include chronic food refusal, weight loss and body image ...distortions. We carried out a genome-wide association study on 1033 AN cases and 3733 pediatric control subjects, all of whom were of European ancestry and were genotyped on the Illumina HumanHap610 platform (Illumina, San Diego, CA, USA). We confirmed that common single-nucleotide polymorphisms (SNPs) within OPRD1 (rs533123, P=0.0015) confer risk for AN, and obtained suggestive evidence that common SNPs near HTR1D (rs7532266, P=0.04) confer risk for restricting-type AN specifically. However, no SNPs reached genome-wide significance in our data, whereas top association signals were detected near ZNF804B, CSRP2BP, NTNG1, AKAP6 and CDH9. In parallel, we performed genome-wide analysis on copy number variations (CNVs) using the signal intensity data from the SNP arrays. We did not find evidence that AN cases have more CNVs than control subjects, nor do they have over-representation of rare or large CNVs. However, we identified several regions with rare CNVs that were only observed in AN cases, including a recurrent 13q12 deletion (1.5 Mb) disrupting SCAS in two cases, and CNVs disrupting the CNTN6/CNTN4 region in several AN cases. In conclusion, our study suggests that both common SNPs and rare CNVs may confer genetic risk to AN. These results point to intriguing genes that await further validation in independent cohorts for confirmatory roles in AN.
Delhi is one of the world's most polluted cities, with very high concentrations of airborne particulate matter. However, little is known about the factors controlling the characteristics of ...wide-range particle number size distributions. Here, new measurements are reported from three field campaigns conducted in winter and pre-monsoon and post-monsoon seasons at the Indian Institute of Technology campus in the south of the city. Particle number size distributions were measured simultaneously, using a scanning mobility particle sizer and a GRIMM optical particle monitor, covering 15 nm to >10 µm diameter. The merged, wide-range size distributions were categorized into the following five size ranges: nucleation (15–20 nm), Aitken (20–100 nm), accumulation (100 nm–1 µm), large fine (1–2.5 µm), and coarse (2.5–10 µm) particles. The ultrafine fraction (15–100 nm) accounts for about 52 % of all particles by number (PN10 is the total particle number from 15 nm to 10 µm) but just 1 % by PM10 volume (PV10 is the total particle volume from 15 nm to 10 µm). The measured size distributions are markedly coarser than most from other parts of the world but are consistent with earlier cascade impactor data from Delhi. Our results suggest substantial aerosol processing by coagulation, condensation, and water uptake in the heavily polluted atmosphere, which takes place mostly at nighttime and in the morning hours. Total number concentrations are highest in winter, but the mode of the distribution is largest in the post-monsoon (autumn) season. The accumulation mode particles dominate the particle volume in autumn and
winter, while the coarse mode dominates in summer. Polar plots show a huge variation between both size fractions in the same season and between seasons for the same size fraction. The diurnal pattern of particle numbers is strongly reflective of a road traffic influence upon concentrations, especially in autumn and winter, although other sources, such as cooking and domestic heating, may influence the evening peak. There is a clear influence of diesel traffic at nighttime, when it is permitted to enter the city, and also indications in the size distribution data of a mode < 15 nm, which is probably attributable to CNG/LPG vehicles. New particle formation appears to be infrequent and is, in this dataset, limited to 1 d in the summer campaign. Our results reveal that the very high emissions of airborne particles in Delhi, particularly from traffic, determine the variation in particle number size distributions.
Over the past 18 months, there have been notable developments in the direct-to-consumer (DTC) genomic testing arena, in particular with regard to issues surrounding governmental regulation in the ...USA. While commentaries continue to proliferate on this topic, actual empirical research remains relatively scant. In terms of DTC genomic testing for disease susceptibility, most of the research has centered on uptake, perceptions and attitudes toward testing among health care professionals and consumers. Only a few available studies have examined actual behavioral response among consumers, and we are not aware of any studies that have examined response to DTC genetic testing for ancestry or for drug response. We propose that further research in this area is desperately needed, despite challenges in designing appropriate studies given the rapid pace at which the field is evolving. Ultimately, DTC genomic testing for common markers and conditions is only a precursor to the eventual cost-effectiveness and wide availability of whole genome sequencing of individuals, although it remains unclear whether DTC genomic information will still be attainable. Either way, however, current knowledge needs to be extended and enhanced with respect to the delivery, impact and use of increasingly accurate and comprehensive individualized genomic data.
Individuals who undergo multiplex direct‐to‐consumer (DTC) genomic testing receive genetic risk results for multiple conditions. To date, research has not investigated the influence of individual ...differences in disease perceptions among consumers on testing outcomes. A total of 2037 participants received DTC genomic testing and completed baseline and follow‐up surveys assessing disease perceptions and health behaviors. Participants were asked to indicate their most feared disease of those tested. Perceived seriousness and controllability of the disease via lifestyle or medical intervention were assessed. Participants most frequently reported heart attack (19.1%) and Alzheimer's disease (18.6%) as their most feared disease. Perceived seriousness and control over the feared disease both influenced response to DTC genomic testing. Greater perceived seriousness and diminished perceived control were associated with higher, but not clinically significant levels of anxiety and distress. In some cases these associations were modified by genetic risk. No significant associations were observed for diet, exercise and screening behaviors. Individual differences in disease perceptions influence psychological outcomes following DTC genomic testing. Higher perceived seriousness may make a consumer more psychologically sensitive to test results and greater perceived control may protect against adverse psychological outcomes. Findings may inform development of educational and counseling services.
The Indian megacity of Delhi suffers from some of the
poorest air quality in the world. While ambient NO2 and particulate
matter (PM) concentrations have received considerable attention in the city,
...high ground-level ozone (O3) concentrations are an often overlooked
component of pollution. O3 can lead to significant ecosystem damage and
agricultural crop losses, and adversely affect human health. During October 2018,
concentrations of speciated non-methane hydrocarbon volatile organic
compounds (C2–C13), oxygenated volatile organic compounds
(o-VOCs), NO, NO2, HONO, CO, SO2, O3, and photolysis rates,
were continuously measured at an urban site in Old Delhi. These observations
were used to constrain a detailed chemical box model utilising the Master
Chemical Mechanism v3.3.1. VOCs and NOx (NO + NO2) were varied
in the model to test their impact on local O3 production rates,
P(O3), which revealed a VOC-limited chemical regime. When only NOx
concentrations were reduced, a significant increase in P(O3) was
observed; thus, VOC co-reduction approaches must also be considered in
pollution abatement strategies. Of the VOCs examined in this work, mean
morning P(O3) rates were most sensitive to monoaromatic compounds,
followed by monoterpenes and alkenes, where halving their concentrations in
the model led to a 15.6 %, 13.1 %, and 12.9 % reduction in
P(O3), respectively. P(O3) was not sensitive to direct changes in
aerosol surface area but was very sensitive to changes in photolysis rates,
which may be influenced by future changes in PM concentrations. VOC and
NOx concentrations were divided into emission source sectors, as
described by the Emissions Database for Global Atmospheric Research (EDGAR) v5.0 Global Air Pollutant Emissions and EDGAR
v4.3.2_VOC_spec inventories, allowing for the
impact of individual emission sources on P(O3) to be investigated.
Reducing road transport emissions only, a common strategy in air pollution
abatement strategies worldwide, was found to increase P(O3), even when
the source was removed in its entirety. Effective reduction in P(O3)
was achieved by reducing road transport along with emissions from combustion
for manufacturing and process emissions. Modelled P(O3) reduced by
∼ 20 ppb h−1 when these combined sources were halved. This study
highlights the importance of reducing VOCs in parallel with NOx and PM
in future pollution abatement strategies in Delhi.
METEOROLOGY, AIR QUALITY, AND HEALTH IN LONDON Bohnenstengel, S. I.; Belcher, S. E.; Aiken, A. ...
Bulletin of the American Meteorological Society,
05/2015, Letnik:
96, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Air quality and heat are strong health drivers, and their accurate assessment and forecast are important in densely populated urban areas. However, the sources and processes leading to high ...concentrations of main pollutants, such as ozone, nitrogen dioxide, and fine and coarse particulate matter, in complex urban areas are not fully understood, limiting our ability to forecast air quality accurately. This paper introduces the Clean Air for London (ClearfLo; www.clearflo.ac.uk) project’s interdisciplinary approach to investigate the processes leading to poor air quality and elevated temperatures.
Within ClearfLo, a large multi-institutional project funded by the U.K. Natural Environment Research Council (NERC), integrated measurements of meteorology and gaseous, and particulate composition/loading within the atmosphere of London, United Kingdom, were undertaken to understand the processes underlying poor air quality. Long-term measurement infrastructure installed at multiple levels (street and elevated), and at urban background, curbside, and rural locations were complemented with high-resolution numerical atmospheric simulations. Combining these (measurement–modeling) enhances understanding of seasonal variations in meteorology and composition together with the controlling processes. Two intensive observation periods (winter 2012 and the Summer Olympics of 2012) focus upon the vertical structure and evolution of the urban boundary layer; chemical controls on nitrogen dioxide and ozone production—in particular, the role of volatile organic compounds; and processes controlling the evolution, size, distribution, and composition of particulate matter. The paper shows that mixing heights are deeper over London than in the rural surroundings and that the seasonality of the urban boundary layer evolution controls when concentrations peak. The composition also reflects the seasonality of sources such as domestic burning and biogenic emissions.
The REgents PARk and Tower Environmental Experiment (REPARTEE) comprised two campaigns in London in October 2006 and October/November 2007. The experiment design involved measurements at a heavily ...trafficked roadside site, two urban background sites and an elevated site at 160-190 m above ground on the BT Tower, supplemented in the second campaign by Doppler lidar measurements of atmospheric vertical structure. A wide range of measurements of airborne particle physical metrics and chemical composition were made as well as measurements of a considerable range of gas phase species and the fluxes of both particulate and gas phase substances. Significant findings include (a) demonstration of the evaporation of traffic-generated nanoparticles during both horizontal and vertical atmospheric transport; (b) generation of a large base of information on the fluxes of nanoparticles, accumulation mode particles and specific chemical components of the aerosol and a range of gas phase species, as well as the elucidation of key processes and comparison with emissions inventories; (c) quantification of vertical gradients in selected aerosol and trace gas species which has demonstrated the important role of regional transport in influencing concentrations of sulphate, nitrate and secondary organic compounds within the atmosphere of London; (d) generation of new data on the atmospheric structure and turbulence above London, including the estimation of mixed layer depths; (e) provision of new data on trace gas dispersion in the urban atmosphere through the release of purposeful tracers; (f) the determination of spatial differences in aerosol particle size distributions and their interpretation in terms of sources and physico-chemical transformations; (g) studies of the nocturnal oxidation of nitrogen oxides and of the diurnal behaviour of nitrate aerosol in the urban atmosphere, and (h) new information on the chemical composition and source apportionment of particulate matter size fractions in the atmosphere of London derived both from bulk chemical analysis and aerosol mass spectrometry with two instrument types.
Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits—specifically reading disability (RD) and ...language impairment (LI)—are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co‐occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome‐wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10−7) and COL4A2 (OR = 1.71, P = 7.59 × 10−7). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10−7). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.
ZNF385D associates with comorbid reading disability and language impairment, as well as overall fiber tract and brain volumes.
To describe consumers' perceptions of genetic counseling services in the context of direct‐to‐consumer personal genomic testing is the purpose of this research. Utilizing data from the Scripps ...Genomic Health Initiative, we assessed direct‐to‐consumer genomic test consumers' utilization and perceptions of genetic counseling services. At long‐term follow‐up, approximately 14 months post‐testing, participants were asked to respond to several items gauging their interactions, if any, with a Navigenics genetic counselor, and their perceptions of those interactions. Out of 1325 individuals who completed long‐term follow‐up, 187 (14.1%) indicated that they had spoken with a genetic counselor. The most commonly given reason for not utilizing the counseling service was a lack of need due to the perception of already understanding one's results (55.6%). The most common reasons for utilizing the service included wanting to take advantage of a free service (43.9%) and wanting more information on risk calculations (42.2%). Among those who utilized the service, a large fraction reported that counseling improved their understanding of their results (54.5%) and genetics in general (43.9%). A relatively small proportion of participants utilized genetic counseling after direct‐to‐consumer personal genomic testing. Among those individuals who did utilize the service, however, a large fraction perceived it to be informative, and thus presumably beneficial.
PDF
