Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak

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A measurement of inclusive ZZ production cross section and constraints on anomalous triple gauge couplings in proton-proton collisions at $\sqrt{s}$ = 8 TeV are presented. A data sample, corresponding to an integrated luminosity of 19.6 inverse-femtobarns was collected with the CMS experiment at the LHC. The measurements are performed in the leptonic decay modes $ZZ \to lll'l'$, where $l = e, \mu$ and $l' = e, \mu, \tau$. The measured total cross section, $\sigma (pp \to ZZ) = 7.7 \pm 0.5 (stat.)^{+0.5}_{-0.4} (syst.) \pm 0.4 (theo.) \pm 0.2 (lum.) pb$ for both Z bosons produced in the mass range $m_Z$ within 60 and 120 GeV, is consistent with standard model predictions. Differential cross sections are measured and well described by the theoretical predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ$\gamma$ couplings at the 95% confidence level: $f_4^Z$ in (-0.004,+0.004), $f_5^Z$ in (-0.005,+0.005), $f_4^\gamma$ in (-0.004,+0.004), and $f_5^\gamma$ in (-0.005,+0.005)

Description and performance of track and primary-vertex reconstruction with the CMS tracker

A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For t (t) over bar events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of p(T) > 0.9GeV is 94% for pseudorapidities of vertical bar eta vertical bar < 0.9 and 85% for 0.9 < vertical bar eta vertical bar < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of p(T) = 100GeV emitted at vertical bar eta vertical bar < 1.4, the resolutions are approximately 2.8% in p(T), and respectively, 10 m m and 30 mu m in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10-12 mu m in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung

Search for excited quarks in the gamma plus jet final state in proton-proton collisions at root s=8 TeV

A search for excited quarks decaying into the gamma + jet final state is presented. The analysis is based on data corresponding to an integrated luminosity of 19.7 fb(-1) collected by the CMS experiment in proton-proton collisions at root s = 8 TeV at the LHC. Events with photons and jets with high transverse momenta are selected and the gamma + jet invariant mass distribution is studied to search for a resonance peak. The 95% confidence level upper limits on the product of cross section and branching fraction are evaluated as a function of the excited quark mass. Limits on excited quarks are presented as a function of their mass and coupling strength; masses below 3.5 TeV are excluded at 95% confidence level for unit couplings to their standard model partners

Search for pair production of third-generation scalar leptoquarks and top squarks in proton-proton collisions at v root s=8 TeV

A search for pair production of third-generation scalar leptoquarks and supersymmetric top quark partners, top squarks, in final states involving tau leptons and bottom quarks is presented. The search uses events from a data sample of proton-proton collisions corresponding to an integrated luminosity of 19.7 fb(-1), collected with the CMS detector at the LHC with root s = 8 TeV. The number of observed events is found to be in agreement with the expected standard model background. Third-generation scalar leptoquarks with masses below 740 GeV are excluded at 95% confidence level, assuming a 100% branching fraction for the leptoquark decay to a tau lepton and a bottom quark. In addition, this mass limit applies directly to top squarks decaying via an R-parity violating coupling. lambda(') (333). The search also considers a similar signature from top squarks undergoing a chargino-mediated decay involving the Rparity violating coupling. lambda(')(3jk). Each top squark decays to a tau lepton, a bottom quark, and two light quarks. Top squarks in this model with masses below 580 GeV are excluded at 95% confidence level. The constraint on the leptoquark mass is the most stringent to date, and this is the first search for top squarks decaying via. lambda(')(3jk)

Performance of the CMS missing transverse momentum reconstruction in pp data at √s= 8 TeV

The performance of missing transverse energy reconstruction algorithms is presented using root s = 8 TeV proton-proton (pp) data collected with the CMS detector. Events with anomalous missing transverse energy are studied, and the performance of algorithms used to identify and remove these events is presented. The scale and resolution for missing transverse energy, including the effects of multiple pp interactions (pileup), are measured using events with an identified Z boson or isolated photon, and are found to be well described by the simulation. Novel missing transverse energy reconstruction algorithms developed specifically to mitigate the effects of large numbers of pileup interactions on the missing transverse energy resolution are presented. These algorithms significantly reduce the dependence of the missing transverse energy resolution on pileup interactions. Finally, an algorithm that provides an estimate of the significance of the missing transverse energy is presented, which is used to estimate the compatibility of the reconstructed missing transverse energy with a zero nominal value

Constraints on the Higgs boson width from off-shell production and decay to Z-boson pairs

Constraints are presented on the total width of the recently discovered Higgs boson, Gamma(H), using its relative on-shell and off-shell production and decay rates to a pair of Z bosons, where one Z boson decays to an electron or muon pair, and the other to an electron, muon, or neutrino pair. The analysis is based on the data collected by the CMS experiment at the LHC in 2011 and 2012, corresponding to integrated luminosities of 5.1 fb(-1) at a center-of-mass energy root s = 7 TeV and 19.7 fb(-1) at root s = 8 TeV. A simultaneous maximum likelihood fit to the measured kinematic distributions near the resonance peak and above the Z-boson pair production threshold leads to an upper limit on the Higgs boson width of Gamma(H) < 22 MeV at a 95% confidence level, which is 5.4 times the expected value in the standard model at the measured mass of m(H) = 125.6 GeV