The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

Search for boosted diphoton resonances in the 10 to 70 GeV mass range using 138 fb−1 of 13 TeV pp collisions with the ATLAS detector

A search for diphoton resonances in the mass range between 10 and 70 GeV with the ATLAS experiment at the Large Hadron Collider (LHC) is presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 138 fb−1 at a centre-of-mass energy of 13 TeV recorded from 2015 to 2018. Previous searches for diphoton resonances at the LHC have explored masses down to 65 GeV, finding no evidence of new particles. This search exploits the particular kinematics of events with pairs of closely spaced photons reconstructed in the detector, allowing examination of invariant masses down to 10 GeV. The presented strategy covers a region previously unexplored at hadron colliders because of the experimental challenges of recording low-energy photons and estimating the backgrounds. No significant excess is observed and the reported limits provide the strongest bound on promptly decaying axion-like particles coupling to gluons and photons for masses between 10 and 70 GeV

Evidence for the charge asymmetry in pp → tt¯ production at s√ = 13 TeV with the ATLAS detector

Inclusive and differential measurements of the top–antitop (tt¯) charge asymmetry Att¯C and the leptonic asymmetry Aℓℓ¯C are presented in proton–proton collisions at s√ = 13 TeV recorded by the ATLAS experiment at the CERN Large Hadron Collider. The measurement uses the complete Run 2 dataset, corresponding to an integrated luminosity of 139 fb−1, combines data in the single-lepton and dilepton channels, and employs reconstruction techniques adapted to both the resolved and boosted topologies. A Bayesian unfolding procedure is performed to correct for detector resolution and acceptance effects. The combined inclusive tt¯ charge asymmetry is measured to be Att¯C = 0.0068 ± 0.0015, which differs from zero by 4.7 standard deviations. Differential measurements are performed as a function of the invariant mass, transverse momentum and longitudinal boost of the tt¯ system. Both the inclusive and differential measurements are found to be compatible with the Standard Model predictions, at next-to-next-to-leading order in quantum chromodynamics perturbation theory with next-to-leading-order electroweak corrections. The measurements are interpreted in the framework of the Standard Model effective field theory, placing competitive bounds on several Wilson coefficients

Study of Z → llγ decays at √s = 8 TeV with the ATLAS detector

This paper presents a study of Z → llγ decays with the ATLAS detector at the Large Hadron Collider. The analysis uses a proton–proton data sample corresponding to an integrated luminosity of 20.2 fb−1 collected at a centre-ofmass energy √s = 8 TeV. Integrated fiducial cross-sections together with normalised differential fiducial cross-sections, sensitive to the kinematics of final-state QED radiation, are obtained. The results are found to be in agreement with stateof-the-art predictions for final-state QED radiation. First measurements of Z → llγ γ decays are also reported

Search for third-generation vector-like leptons in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for vector-like leptons in multilepton (two, three, or four-or-more electrons plus muons) final states with zero or more hadronic τ-lepton decays is presented. The search is performed using a dataset corresponding to an integrated luminosity of 139 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the LHC. To maximize the separation of signal and background, a machine-learning classifier is used. No excess of events is observed beyond the Standard Model expectation. Using a doublet vector-like lepton model, vector-like leptons coupling to third-generation Standard Model leptons are excluded in the mass range from 130 GeV to 900 GeV at the 95% confidence level, while the highest excluded mass is expected to be 970 GeV

Search for heavy Higgs bosons with flavour-violating couplings in multi-lepton plus b-jets final states in pp collisions at 13 TeV with the ATLAS detector

A search for new heavy scalars with flavour-violating decays in final states with multiple leptons and b-tagged jets is presented. The results are interpreted in terms of a general two-Higgs-doublet model involving an additional scalar with couplings to the top-quark and the three up-type quarks (ρtt, ρtc, and ρtu). The targeted signals lead to final states with either a same-sign top-quark pair, three top-quarks, or four top-quarks. The search is based on a data sample of proton-proton collisions at √s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Events are categorised depending on the multiplicity of light charged leptons (electrons or muons), total lepton charge, and a deep-neural-network output to enhance the purity of each of the signals. Masses of an additional scalar boson mH between 200 − 630 GeV with couplings ρtt = 0.4, ρtc = 0.2, and ρtu = 0.2 are excluded at 95% confidence level. Additional interpretations are provided in models of R-parity violating supersymmetry, motivated by the recent flavour and (g − 2)μ anomalies

Search for a new heavy scalar particle decaying into a Higgs boson and a new scalar singlet in final states with one or two light leptons and a pair of τ-leptons with the ATLAS detector

A search for a new heavy scalar particle X decaying into a Standard Model (SM) Higgs boson and a new singlet scalar particle S is presented. The search uses a proton-proton (pp) collision data sample with an integrated luminosity of 140 fb−1 recorded at a centre-of-mass energy of s√ = 13 TeV with the ATLAS detector at the Large Hadron Collider. The most sensitive mass parameter space is explored in X mass ranging from 500 to 1500 GeV, with the corresponding S mass in the range 200–500 GeV. The search selects events with two hadronically decaying τ-lepton candidates from H → τ+τ− decays and one or two light leptons (ℓ = e, μ) from S → VV (V = W, Z) decays while the remaining V boson decays hadronically or to neutrinos. A multivariate discriminant based on event kinematics is used to separate the signal from the background. No excess is observed beyond the expected SM background and 95% confidence level upper limits between 72 fb and 542 fb are derived on the cross-section σ(pp → X → SH) assuming the same SM-Higgs boson-like decay branching ratios for the S → VV decay. Upper limits on the visible cross-sections σ(pp → X → SH → WWττ) and σ(pp → X → SH → ZZττ) are also set in the ranges 3–26 fb and 6–33 fb, respectively

Search for leptoquark pair production decaying into te−te¯ + or tμ−t¯μ+ in multi-lepton final states in pp collisions at √s = 13 TeV with the ATLAS detector

A search for leptoquark pair production decaying into te−te¯ + or tμ−t¯μ+ in final states with multiple leptons is presented. The search is based on a dataset of pp collisions at √s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Four signal regions, with the requirement of at least three light leptons (electron or muon) and at least two jets out of which at least one jet is identified as coming from a b-hadron, are considered based on the number of leptons of a given flavour. The main background processes are estimated using dedicated control regions in a simultaneous fit with the signal regions to data. No excess above the Standard Model background prediction is observed and 95% confidence level limits on the production cross section times branching ratio are derived as a function of the leptoquark mass. Under the assumption of exclusive decays into te− (tμ−), the corresponding lower limit on the scalar mixed-generation leptoquark mass mLQd mix is at 1.58 (1.59) TeV and on the vector leptoquark mass mU˜1 at 1.67 (1.67) TeV in the minimal coupling scenario and at 1.95 (1.95) TeV in the Yang–Mills scenario

Measurement of diferential cross-sections in tt¯ and tt¯+jets production in the lepton+jets fnal state in pp collisions at √s = 13 TeV using 140 fb−1 of ATLAS data

Diferential cross-sections for top-quark pair production, inclusively and in association with jets, are measured in pp collisions at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC using an integrated luminosity of 140 fb−1. The events are selected with one charged lepton (electron or muon) and at least four jets. The differential cross-sections are presented at particle level as functions of several jet observables, including angular correlations, jet transverse momenta and invariant masses of the jets in the final state, which characterise the kinematics and dynamics of the top-antitop system and the hard QCD radiation in the system with associated jets. The typical precision is 5%–15% for the absolute differential cross-sections and 2%–4% for the normalised differential cross-sections. Next-to-leading-order and next-to-next-to-leading-order QCD predictions are found to provide an adequate description of the rate and shape of the jet-angular observables. The description of the transverse momentum and invariant mass observables is improved when next-to-next-to-leading-order QCD corrections are included