Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Advance in photochemistry

+566hlm.;23c

An Investigation of the Dark Formation of Nitrous Acid in Environmental Chambers

The formation of nitrous acid (HONO) in the dark from initial concentrations of NO2 of 0.1-20 ppm in air, and the concurrent disappearance of NO2, were monitored quantitatively by UV differential optical absorption spectroscopy in two different environmental chambers of ca.4300- and 5800-L volume (both with surface/volume ratios of 3.4 m-1). In these environmental chambers the initial HONO formation rate was first order in the NO2 concentration and increased with the water vapor concentration. However, the HONO formation rate was independent of the NO concentration and relatively insensitive to temperature. The initial pseudo-first-order consumption rate of NO2 was (2.8 ± 1.2) × 10-4 min-1 in the 5800-L Teflon-coated evacuable chamber and (1.6 ± 0.5) × 10-4 min-1 in a 4300-L all-Teflon reaction chamber at ca.300 K and ca.50% RH. The initial HONO yields were ca.40-50% of the NO2 reacted in the evacuable chamber and ca.10-30% in the all-Teflon chamber. Nitric oxide formation was observed during the later stages of the reaction in the evacuable chamber, but ca.50% of the nitrogen could not be accounted for, and gas phase HNO3 was not detected. The implications of these data concerning radical sources in environmental chamber irradiations of NOx- organic-air mixtures, and of HONO formation in polluted atmospheres, are discussed

Crystallization of helix pomatia agglutinin (HPA), a protein from the edible snail

Crystals of Helix pomatia agglutinin (HPA) have been grown by the hanging-drop technique using polyethylene glycol as the precipitant at 293 K. Over a period of one to two weeks the crystals grew to maximum dimensions of 0.10 × 0.05 × 0.02 mm. The crystals belong to space group P6322, with unit-cell dimensions a = b = 63.3, c = 105.2 Å and Z = 12 identical monomers of Mr = 13 kDa, aggregating into two 78 kDa hexameric protein molecules per unit cell, each with symmetry 32 (D3). The diffraction pattern extends to 3.6 Å at 293 K