Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Development of a Trigger for Proton-Charm Femtoscopy with ALICE for the LHC Run3

In this CERN Summer Student project, the feasibility of a proton-charm hadron trigger for femtoscopic studies in proton-proton collisions with ALICE has been investigated for the upcoming LHC Run3. After a short introduction to femtoscopy and the charm hadron selection, this report presents the results concerning the impact of the topological charm hadron selections on the trigger. The studies have been performed with Monte Carlo simulations of the ALICE detector using the PYTHIA generator as an input. Lastly, the implementation of the trigger in the ALICE Run3 analysis framework O2 is briefly discussed

Analysis of Shared Heritability in Common Disorders of the Brain

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology

Measurement of inclusive J/ψ\psi pair production cross section in pp collisions at s=13\sqrt{s} = 13 TeV

International audienceThe production cross section of inclusive J/$\psi$ pairs in pp collisions at a centre-of-mass energy $\sqrt{s} = 13$ TeV is measured with ALICE. The measurement is performed for J/$\psi$ in the rapidity interval $2.5 0$. The production cross section of inclusive J/$\psi$ pairs is reported to be $10.3 \pm 2.3 {\rm (stat.)} \pm 1.3 {\rm (syst.)}$ nb in this kinematic interval. The contribution from non-prompt J/$\psi$ (i.e. originated from beauty-hadron decays) to the inclusive sample is evaluated. The results are discussed and compared with data

Inclusive and multiplicity dependent production of electrons from heavy-flavour hadron decays in pp and p−-Pb collisions

International audienceMeasurements of the production of electrons from heavy-flavour hadron decays in pp collisions at $\sqrt{s} = 13$ TeV at midrapidity with the ALICE detector are presented down to a transverse momentum ($p_{\rm T}$) of 0.2 GeV$/c$ and up to $p_{\rm T} = 35$ GeV$/c$, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p$-$Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the $p_{\rm T}$ range $0.5 < p_{\rm T} < 26$ GeV$/c$ at $\sqrt{s_{\rm NN}} = 8.16$ TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p$-$Pb collisions grow faster than linear with the self-normalised multiplicity. A strong $p_{\rm T}$ dependence is observed in pp collisions, where the yield of high-$p_{\rm T}$ electrons increases faster as a function of multiplicity than the one of low-$p_{\rm T}$ electrons. The measurement in p$-$Pb collisions shows no $p_{\rm T}$ dependence within uncertainties. The self-normalised yields in pp and p$-$Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations

Observation of medium-induced yield enhancement and acoplanarity broadening of low-pTp_\mathrm{T} jets from measurements in pp and central Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceThe ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high $p_{\rm T}$) hadron trigger in proton$-$proton and central Pb$-$Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$ TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb$-$Pb collisions. Recoil jet distributions are reported for jet resolution parameter $R=0.2$, 0.4, and 0.5 in the range $7 < p_{\rm T,jet} < 140$ GeV$/c$ and trigger$-$recoil jet azimuthal separation $\pi/2 < \Delta\varphi < \pi$. The measurements exhibit a marked medium-induced jet yield enhancement at low $p_{\rm T}$ and at large azimuthal deviation from $\Delta\varphi\sim\pi$. The enhancement is characterized by its dependence on $\Delta\varphi$, which has a slope that differs from zero by 4.7$\sigma$. Comparisons to model calculations incorporating different formulations of jet quenching are reported. These comparisons indicate that the observed yield enhancement arises from the response of the QGP medium to jet propagation

Probing the Chiral Magnetic Wave with charge-dependent flow measurements in Pb-Pb collisions at the LHC

International audienceThe Chiral Magnetic Wave (CMW) phenomenon is essential to provide insights into the strong interaction in QCD, the properties of the quark-gluon plasma, and the topological characteristics of the early universe, offering a deeper understanding of fundamental physics in high-energy collisions. Measurements of the charge-dependent anisotropic flow coefficients are studied in Pb-Pb collisions at center-of-mass energy per nucleon-nucleon collision $\sqrt{s_{\mathrm{NN}}}=$ 5.02 TeV to probe the CMW. In particular, the slope of the normalized difference in elliptic ($v_{2}$) and triangular ($v_{3}$) flow coefficients of positively and negatively charged particles as a function of their event-wise normalized number difference, is reported for inclusive and identified particles. The slope $r_{3}^{\rm Norm}$ is found to be larger than zero and to have a magnitude similar to $r_{2}^{\rm Norm}$, thus pointing to a large background contribution for these measurements. Furthermore, $r_{2}^{\rm Norm}$ can be described by a blast wave model calculation that incorporates local charge conservation. In addition, using the event shape engineering technique yields a fraction of CMW ($f_{\rm CMW}$) contribution to this measurement which is compatible with zero. This measurement provides the very first upper limit for $f_{\rm CMW}$, and in the 10-60% centrality interval it is found to be 26% (38%) at 95% (99.7%) confidence level

Charged-particle production as a function of the relative transverse activity classifier in pp, p−-Pb, and Pb−-Pb collisions at the LHC

International audienceMeasurements of charged-particle production in pp, p$-$Pb, and Pb$-$Pb collisions in the toward, away, and transverse regions with the ALICE detector are discussed. These regions are defined event-by-event relative to the azimuthal direction of the charged trigger particle, which is the reconstructed particle with the largest transverse momentum ($p_{\mathrm{T}}^{\rm trig}$) in the range $8<p_{\mathrm{T}}^{\rm trig}<15$ GeV$/c$. The toward and away regions contain the primary and recoil jets, respectively; both regions are accompanied by the underlying event (UE). In contrast, the transverse region perpendicular to the direction of the trigger particle is dominated by the so-called UE dynamics, and includes also contributions from initial- and final-state radiation. The relative transverse activity classifier, $R_{\mathrm{T}}=N_{\mathrm{ch}}^{\mathrm{T}}/\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle$, is used to group events according to their UE activity, where $N_{\mathrm{ch}}^{\mathrm{T}}$ is the charged-particle multiplicity per event in the transverse region and $\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle$ is the mean value over the whole analysed sample. The energy dependence of the $R_{\mathrm{T}}$ distributions in pp collisions at $\sqrt{s}=2.76$, 5.02, 7, and 13 TeV is reported, exploring the Koba-Nielsen-Olesen (KNO) scaling properties of the multiplicity distributions. The first measurements of charged-particle $p_{\rm T}$ spectra as a function of $R_{\mathrm{T}}$ in the three azimuthal regions in pp, p$-$Pb, and Pb$-$Pb collisions at $\sqrt{s_{\rm NN}}=5.02$ TeV are also reported. Data are compared with predictions obtained from the event generators PYTHIA 8 and EPOS LHC. This set of measurements is expected to contribute to the understanding of the origin of collective-like effects in small collision systems (pp and p$-$Pb)