Rare disruptive variants in the DISC1 Interactome and Regulome : association with cognitive ability and schizophrenia

Schizophrenia (SCZ), bipolar disorder (BD) and recurrent major depressive disorder (rMDD) are common psychiatric illnesses. All have been associated with lower cognitive ability, and show evidence of genetic overlap and substantial evidence of pleiotropy with cognitive function and neuroticism. Disrupted in schizophrenia 1 (DISC1) protein directly interacts with a large set of proteins (DISC1 Interactome) that are involved in brain development and signaling. Modulation of DISC1 expression alters the expression of a circumscribed set of genes (DISC1 Regulome) that are also implicated in brain biology and disorder. Here we report targeted sequencing of 59 DISC1 Interactome genes and 154 Regulome genes in 654 psychiatric patients and 889 cognitively-phenotyped control subjects, on whom we previously reported evidence for trait association from complete sequencing of the DISC1 locus. Burden analyses of rare and singleton variants predicted to be damaging were performed for psychiatric disorders, cognitive variables and personality traits. The DISC1 Interactome and Regulome showed differential association across the phenotypes tested. After family-wise error correction across all traits (FWERacross), an increased burden of singleton disruptive variants in the Regulome was associated with SCZ (FWERacross P=0.0339). The burden of singleton disruptive variants in the DISC1 Interactome was associated with low cognitive ability at age 11 (FWERacross P=0.0043). These results identify altered regulation of schizophrenia candidate genes by DISC1 and its core Interactome as an alternate pathway for schizophrenia risk, consistent with the emerging effects of rare copy number variants associated with intellectual disability.Peer reviewe

First Measurement of the Charge Asymmetry in Beauty-Quark Pair Production

The difference in the angular distributions between beauty quarks and antiquarks, referred to as the charge asymmetry, is measured for the first time in b (b) over bar pair production at a hadron collider. The data used correspond to an integrated luminosity of 1.0 fb(-1) collected at 7 TeV center-of-mass energy in proton-proton collisions with the LHCb detector. The measurement is performed in three regions of the invariant mass of the b (b) over bar system. The results obtained are A(C)(b (b) over bar) (40 10(5) GeV/c(2)) = 1.6 +/- 1.7 +/- 0.6%,where A(C)(b (b) over bar) is defined as the asymmetry in the difference in rapidity between jets formed from the beauty quark and antiquark, where in each case the first uncertainty is statistical and the second systematic. The beauty jets are required to satisfy 2 20 GeV, and have an opening angle in the transverse plane Delta phi > 2.6 rad. These measurements are consistent with the predictions of the standard model

Observation of B+c → D0K+ decays

Using proton-proton collision data corresponding to an integrated luminosity of 3.0 fb−1, recorded by the LHCb detector at center-of-mass energies of 7 and 8 TeV, the B+ c → D0K+ decay is observed with a statistical significance of 5.1 standard deviations. By normalizing to B+ → D¯ 0π+ decays, a measurement of the branching fraction multiplied by the production rates for B+ c relative to B+ mesons in the LHCb acceptance is obtained, R D 0 K = ( f c / f u ) × B ( B + c → D 0 K + ) = ( 9. 3 + 2.8 − 2.5 ± 0.6 ) × 10 − 7, where the first uncertainty is statistical and the second is systematic. This decay is expected to proceed predominantly through weak annihilation and penguin amplitudes, and is the first B+ c decay of this nature to be observed

Updated measurements of exclusive J/ψ and ψ(2S) production cross-sections in pp collisions at √s = 7 TeV

The differential cross-section as a function of rapidity has been measured for the exclusive production of J/ψ and ψ(2S) mesons in proton–proton collisions at √s = 7 TeV, using data collected by the LHCb experiment, corresponding to an integrated luminosity of 930 pb−1. The cross-sections times branching fractions to two muons having pseudorapidities between 2.0 and 4.5 are measured to be where the first uncertainty is statistical and the second is systematic. The measurements agree with next-to-leading order QCD predictions as well as with models that include saturation effects

Observation of the decay Λ _b ⁰ → ψ(2S)pπ⁻

International audienceThe Cabibbo-suppressed decay Λ$_{b}^{0}$  → ψ(2S)pπ$^{−}$ is observed for the first time using a data sample collected by the LHCb experiment in proton-proton collisions corresponding to 1.0, 2.0 and 1.9 fb$^{−1}$ of integrated luminosity at centre-of-mass energies of 7, 8 and 13 TeV, respectively. The ψ(2S) mesons are reconstructed in the μ$^{+}$μ$^{−}$ final state. The branching fraction with respect to that of the Λ$_{b}^{0}$  → ψ(2S)pK$^{−}$ decay mode is measured to b

Measurement of the B_{s}^{0}→μ^{+}μ^{-} Branching Fraction and Effective Lifetime and Search for B^{0}→μ^{+}μ^{-} Decays.

A search for the rare decays B_{s}^{0}→μ^{+}μ^{-} and B^{0}→μ^{+}μ^{-} is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4  fb^{-1}. An excess of B_{s}^{0}→μ^{+}μ^{-} decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(B_{s}^{0}→μ^{+}μ^{-})=(3.0±0.6_{-0.2}^{+0.3})×10^{-9}, where the first uncertainty is statistical and the second systematic. The first measurement of the B_{s}^{0}→μ^{+}μ^{-} effective lifetime, τ(B_{s}^{0}→μ^{+}μ^{-})=2.04±0.44±0.05  ps, is reported. No significant excess of B^{0}→μ^{+}μ^{-} decays is found, and a 95% confidence level upper limit, B(B^{0}→μ^{+}μ^{-})<3.4×10^{-10}, is determined. All results are in agreement with the standard model expectations

Measurement of the B0s→μ+μ− Branching Fraction and Effective Lifetime and Search for B0→μ+μ− Decays

See paper for full list of authors - All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2017-001.html - Submitted to Phys. Rev. Lett.International audienceA search for the rare decays B0s→μ+μ− and B0→μ+μ− is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4 fb−1. An excess of B0s→μ+μ− decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(B0s→μ+μ−)=(3.0±0.6+0.3−0.2)×10−9, where the first uncertainty is statistical and the second systematic. The first measurement of the B0s→μ+μ− effective lifetime, τ(B0s→μ+μ−)=2.04±0.44±0.05 ps, is reported. No significant excess of B0→μ+μ− decays is found and a 95 % confidence level upper limit, B(B0→μ+μ−)<3.4×10−10, is determined. All results are in agreement with the Standard Model expectations

Search for Lepton-Universality Violation in B^{+}→K^{+}ℓ^{+}ℓ^{-} Decays.

A measurement of the ratio of branching fractions of the decays B^{+}→K^{+}μ^{+}μ^{-} and B^{+}→K^{+}e^{+}e^{-} is presented. The proton-proton collision data used correspond to an integrated luminosity of 5.0  fb^{-1} recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range 1.1<q^{2}<6.0  GeV^{2}/c^{4} the ratio of branching fractions is measured to be R_{K}=0.846_{-0.054}^{+0.060}_{-0.014}^{+0.016}, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of R_{K} to date and is compatible with the standard model at the level of 2.5 standard deviations

First measurement of the CPCP-violating phase φsdd‾φ_s^{d\overline{d}} in Bs0→(K+π−)(K−π+)B_s^0\to(K^+π^-)(K^-π^+) decays

A flavour-tagged decay-time-dependent amplitude analysis of $B_s^0\to(K^+\pi^-)(K^-\pi^+)$ decays is presented in the $K^{\pm}\pi^{\mp}$ mass range from 750 to 1600 MeV$/c^2$. The analysis uses $pp$ collision data collected with the LHCb detector at centre-of-mass energies of $7$ and $8$ TeV, corresponding to an integrated luminosity of $3.0$ fb$^{-1}$. Several quasi-two-body decay modes are considered, corresponding to $K^{\pm}\pi^{\mp}$ combinations with spin 0, 1 and 2, which are dominated by the $K_0^*(800)^0$ and $K_0^*(1430)^0$, the $K^*(892)^0$ and the $K_2^*(1430)^0$ resonances, respectively. The longitudinal polarisation fraction for the $B_s^0\to K^*(892)^0\overline{K}^*(892)^0$ decay is measured as $f_L=0.208 \pm 0.032 \pm 0.046$, where the first uncertainty is statistical and the second is systematic. The first measurement of the mixing-induced $CP$-violating phase, $\phi_s^{d\overline{d}}$, in $b\to d\overline{d}s$ transitions is performed, yielding a value of $\phi_s^{d\overline{d}}=-0.10$ $\pm$ $0.13$ (stat) $\pm$ $0.14$ (syst) rad

Measurement of the Ratio of the B-0 -> D*(-)iota(+)v(iota) and B-0 -> D*(-) mu(+)v(mu) Branching Fractions Using Three-Prong tau-Lepton Decays

The ratio of branching fractions ${\cal{R}}(D^{*-})\equiv {\cal{B}}(B^0 \to D^{*-} \tau^+ \nu_{\tau})/{\cal{B}}(B^0 \to D^{*-} \mu^+\nu_{\mu})$ is measured using a data sample of proton-proton collisions collected with the LHCb detector at center-of-mass energies of 7 and 8 Tev, corresponding to an integrated luminosity of 3$~$fb$^{-1}$. For the first time ${\cal{R}}(D^{*-})$ is determined using the $\tau$ lepton decays with three charged pions in the final state. The $B^0 \to D^{*-} \tau^+\nu_{\tau}$ yield is normalized to that of the $B^0\to D^{*-} \pi^+\pi^-\pi^+$ mode, providing a measurement of ${\cal{B}}(B^0\to D^{*-}\tau^+\nu_{\tau})/{\cal{B}}(B^0\to D^{*-}\pi^+\pi^-\pi^+) = 1.97 \pm 0.13 \pm 0.18$, where the first uncertainty is statistical and the second systematic. The value of ${\cal{B}}(B^0 \to D^{*-} \tau^+ \nu_{\tau}) = (1.42 \pm 0.094 \pm 0.129 \pm 0.054)\%$ is obtained, where the third uncertainty is due to the limited knowledge of the branching fraction of the normalization mode. Using the well-measured branching fraction of the $B^0 \to D^{*-} \mu^+\nu_{\mu}$ decay, a value of ${\cal{R}}(D^{*-}) = 0.291 \pm 0.019 \pm 0.026 \pm 0.013$ is established, where the third uncertainty is due to the limited knowledge of the branching fractions of the normalization and $B^0\to D^{*-}\mu^+\nu_{\mu}$ modes. This measurement is in agreement with the Standard Model prediction and with previous results.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2017-017.htm