Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Measurements of the branching fractions of B+→ppK+ decays

The branching fractions of the decay B+ → pp̄K+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component Mpp̄ < 2.85 GeV/c2 and the branching fractions via the resonant cc̄ states η c(1S) and ψ(2S) relative to the decay via a J/ψ intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained

Model-independent evidence for J/ψpJ/\psi p contributions to Λb0→J/ψpK−\Lambda_b^0\to J/\psi p K^- decays

The data sample of $\Lambda_b^0\to J/\psi p K^-$ decays acquired with the LHCb detector from 7 and 8~TeV $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$, is inspected for the presence of $J/\psi p$ or $J/\psi K^-$ contributions with minimal assumptions about $K^- p$ contributions. It is demonstrated at more than 9 standard deviations that $\Lambda_b^0\to J/\psi p K^-$ decays cannot be described with $K^- p$ contributions alone, and that $J/\psi p$ contributions play a dominant role in this incompatibility. These model-independent results support the previously obtained model-dependent evidence for $P_c^+\to J/\psi p$ charmonium-pentaquark states in the same data sample.Comment: 21 pages, 12 figures (including the supplemental section added at the end

Differential branching fraction and angular analysis of Λb0→Λμ+μ−\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^- decays

The differential branching fraction of the rare decay $\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-$ is measured as a function of $q^{2}$, the square of the dimuon invariant mass. The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of 3.0 \mbox{ fb}^{-1}, collected by the LHCb experiment. Evidence of signal is observed in the $q^2$ region below the square of the $J/\psi$ mass. Integrating over 15 < q^{2} < 20 \mbox{ GeV}^2/c^4 the branching fraction is measured as d\mathcal{B}(\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-)/dq^2 = (1.18 ^{+ 0.09} _{-0.08} \pm 0.03 \pm 0.27) \times 10^{-7} ( \mbox{GeV}^{2}/c^{4})^{-1}, where the uncertainties are statistical, systematic and due to the normalisation mode, $\Lambda^{0}_{b} \rightarrow J/\psi \Lambda$, respectively. In the $q^2$ intervals where the signal is observed, angular distributions are studied and the forward-backward asymmetries in the dimuon ($A^{l}_{\rm FB}$) and hadron ($A^{h}_{\rm FB}$) systems are measured for the first time. In the range 15 < q^2 < 20 \mbox{ GeV}^2/c^4 they are found to be A^{l}_{\rm FB} = -0.05 \pm 0.09 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)} and A^{h}_{\rm FB} = -0.29 \pm 0.07 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)}.Comment: 27 pages, 10 figures, Erratum adde

Measurement of the mass and lifetime of the Ωb−\Omega_b^- baryon

A proton-proton collision data sample, corresponding to an integrated luminosity of 3 fb$^{-1}$ collected by LHCb at $\sqrt{s}=7$ and 8 TeV, is used to reconstruct $63\pm9$ $\Omega_b^-\to\Omega_c^0\pi^-$, $\Omega_c^0\to pK^-K^-\pi^+$ decays. Using the $\Xi_b^-\to\Xi_c^0\pi^-$, $\Xi_c^0\to pK^-K^-\pi^+$ decay mode for calibration, the lifetime ratio and absolute lifetime of the $\Omega_b^-$ baryon are measured to be \begin{align*} \frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\ \tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the uncertainties are statistical, systematic and from the calibration mode (for $\tau_{\Omega_b^-}$ only). A measurement is also made of the mass difference, $m_{\Omega_b^-}-m_{\Xi_b^-}$, and the corresponding $\Omega_b^-$ mass, which yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2. \end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, 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-2016-008.htm

Study of B−→DK−π+π−B^{-}\to DK^-\pi^+\pi^- and B−→Dπ−π+π−B^-\to D\pi^-\pi^+\pi^- decays and determination of the CKM angle γ\gamma

We report a study of the suppressed $B^-\to DK^-\pi^+\pi^-$ and favored $B^-\to D\pi^-\pi^+\pi^-$ decays, where the neutral $D$ meson is detected through its decays to the $K^{\mp}\pi^{\pm}$ and CP-even $K^+K^-$ and $\pi^+\pi^-$ final states. The measurement is carried out using a proton-proton collision data sample collected by the LHCb experiment, corresponding to an integrated luminosity of 3.0~fb$^{-1}$. We observe the first significant signals in the CP-even final states of the $D$ meson for both the suppressed $B^-\to DK^-\pi^+\pi^-$ and favored $B^-\to D\pi^-\pi^+\pi^-$ modes, as well as in the doubly Cabibbo-suppressed $D\to K^+\pi^-$ final state of the $B^-\to D\pi^-\pi^+\pi^-$ decay. Evidence for the ADS suppressed decay $B^{-}\to DK^-\pi^+\pi^-$, with $D\to K^+\pi^-$, is also presented. From the observed yields in the $B^-\to DK^-\pi^+\pi^-$, $B^-\to D\pi^-\pi^+\pi^-$ and their charge conjugate decay modes, we measure the value of the weak phase to be $\gamma=(74^{+20}_{-19})^{\rm o}$. This is one of the most precise single-measurement determinations of $\gamma$ to date.Comment: 22 pages, 9 figures; 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-2015-020.htm

BB flavour tagging using charm decays at the LHCb experiment

An algorithm is described for tagging the flavour content at production of neutral $B$ mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a $B$ meson with the charge of a reconstructed secondary charm hadron from the decay of the other $b$ hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes $B^+ \to J/\psi \, K^+$ and $B^0 \to J/\psi \, K^{*0}$ using $3.0\mathrm{\,fb}^{-1}$ of data collected by the LHCb experiment at $pp$ centre-of-mass energies of $7\mathrm{\,TeV}$ and $8\mathrm{\,TeV}$. Its tagging power on these samples of $B \to J/\psi \, X$ decays is $(0.30 \pm 0.01 \pm 0.01) \%$.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm

Study of charmonium production in b -hadron decays and first evidence for the decay Bs0

Using decays to φ-meson pairs, the inclusive production of charmonium states in b-hadron decays is studied with pp collision data corresponding to an integrated luminosity of 3.0 fb−1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. Denoting byBC ≡ B(b → C X) × B(C → φφ) the inclusive branching fraction of a b hadron to a charmonium state C that decays into a pair of φ mesons, ratios RC1C2 ≡ BC1 /BC2 are determined as Rχc0ηc(1S) = 0.147 ± 0.023 ± 0.011, Rχc1ηc(1S) =0.073 ± 0.016 ± 0.006, Rχc2ηc(1S) = 0.081 ± 0.013 ± 0.005,Rχc1 χc0 = 0.50 ± 0.11 ± 0.01, Rχc2 χc0 = 0.56 ± 0.10 ± 0.01and Rηc(2S)ηc(1S) = 0.040 ± 0.011 ± 0.004. Here and below the first uncertainties are statistical and the second systematic.Upper limits at 90% confidence level for the inclusive production of X(3872), X(3915) and χc2(2P) states are obtained as RX(3872)χc1 < 0.34, RX(3915)χc0 < 0.12 andRχc2(2P)χc2 < 0.16. Differential cross-sections as a function of transverse momentum are measured for the ηc(1S) andχc states. The branching fraction of the decay B0s → φφφ is measured for the first time, B(B0s → φφφ) = (2.15±0.54±0.28±0.21B)×10−6. Here the third uncertainty is due to the branching fraction of the decay B0s → φφ, which is used for normalization. No evidence for intermediate resonances is seen. A preferentially transverse φ polarization is observed.The measurements allow the determination of the ratio of the branching fractions for the ηc(1S) decays to φφ and p p asB(ηc(1S)→ φφ)/B(ηc(1S)→ p p) = 1.79 ± 0.14 ± 0.32

Search for the rare decays B0→J/ψγB^{0}\to J/\psi \gamma and Bs0→J/ψγB^{0}_{s} \to J/\psi \gamma

A search for the rare decay of a $B^{0}$ or $B^{0}_{s}$ meson into the final state $J/\psi\gamma$ is performed, using data collected by the LHCb experiment in $pp$ collisions at $\sqrt{s}=7$ and $8$ TeV, corresponding to an integrated luminosity of 3 fb$^{-1}$. The observed number of signal candidates is consistent with a background-only hypothesis. Branching fraction values larger than $1.7\times 10^{-6}$ for the $B^{0}\to J/\psi\gamma$ decay mode are excluded at 90% confidence level. For the $B^{0}_{s}\to J/\psi\gamma$ decay mode, branching fraction values larger than $7.4\times 10^{-6}$ are excluded at 90% confidence level, this is the first branching fraction limit for this decay.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-2015-044.htm