Synaptic, transcriptional and chromatin genes disrupted in autism.

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones

Search for Nonresonant Pair Production of Highly Energetic Higgs Bosons Decaying to Bottom Quarks

International audienceA search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb-1 collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ2V, excluding κ2V=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values