Allelic Heterogeneity at the CRP Locus Identified by Whole-Genome Sequencing in Multi-ancestry Cohorts

Whole-genome sequencing (WGS) can improve assessment of low-frequency and rare variants, particularly in non-European populations that have been underrepresented in existing genomic studies. The genetic determinants of C-reactive protein (CRP), a biomarker of chronic inflammation, have been extensively studied, with existing genome-wide association studies (GWASs) conducted in >200,000 individuals of European ancestry. In order to discover novel loci associated with CRP levels, we examined a multi-ancestry population (n = 23,279) with WGS (∼38× coverage) from the Trans-Omics for Precision Medicine (TOPMed) program. We found evidence for eight distinct associations at the CRP locus, including two variants that have not been identified previously (rs11265259 and rs181704186), both of which are non-coding and more common in individuals of African ancestry (∼10% and ∼1% minor allele frequency, respectively, and rare or monomorphic in 1000 Genomes populations of East Asian, South Asian, and European ancestry). We show that the minor (G) allele of rs181704186 is associated with lower CRP levels and decreased transcriptional activity and protein binding in vitro, providing a plausible molecular mechanism for this African ancestry-specific signal. The individuals homozygous for rs181704186-G have a mean CRP level of 0.23 mg/L, in contrast to individuals heterozygous for rs181704186 with mean CRP of 2.97 mg/L and major allele homozygotes with mean CRP of 4.11 mg/L. This study demonstrates the utility of WGS in multi-ethnic populations to drive discovery of complex trait associations of large effect and to identify functional alleles in noncoding regulatory regions

Measurement of CP observables in B± → D(⁎)K± and B± → D(⁎)π± decays

Measurements of CP observables in B ± →D (⁎) K ± and B ± →D (⁎) π ± decays are presented, where D (⁎) indicates a neutral D or D ⁎ meson that is an admixture of D (⁎)0 and D¯ (⁎)0 states. Decays of the D ⁎ meson to the Dπ 0 and Dγ final states are partially reconstructed without inclusion of the neutral pion or photon, resulting in distinctive shapes in the B candidate invariant mass distribution. Decays of the D meson are fully reconstructed in the K ± π ∓ , K + K − and π + π − final states. The analysis uses a sample of charged B mesons produced in pp collisions collected by the LHCb experiment, corresponding to an integrated luminosity of 2.0, 1.0 and 2.0 fb −1 taken at centre-of-mass energies of s=7, 8 and 13 TeV, respectively. The study of B ± →D ⁎ K ± and B ± →D ⁎ π ± decays using a partial reconstruction method is the first of its kind, while the measurement of B ± →DK ± and B ± →Dπ ± decays is an update of previous LHCb measurements. The B ± →DK ± results are the most precise to date

EuFe2_2As2_2 under high pressure: an antiferromagnetic bulk superconductor

We report the ac magnetic susceptibility $\chi_{ac}$ and resistivity $\rho$ measurements of EuFe$_2$As$_2$ under high pressure $P$. By observing nearly 100% superconducting shielding and zero resistivity at $P$ = 28 kbar, we establish that $P$-induced superconductivity occurs at $T_c \sim$~30 K in EuFe$_2$As$_2$. $\rho$ shows an anomalous nearly linear temperature dependence from room temperature down to $T_c$ at the same $P$. $\chi_{ac}$ indicates that an antiferromagnetic order of Eu$^{2+}$ moments with $T_N \sim$~20 K persists in the superconducting phase. The temperature dependence of the upper critical field is also determined.Comment: To appear in J. Phys. Soc. Jpn., Vol. 78 No.

Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits

Measurement of CPCP asymmetries in D±→η′π±D^{\pm}\rightarrow \eta^{\prime} \pi^{\pm} and Ds±→η′π±D_s^{\pm}\rightarrow \eta^{\prime} \pi^{\pm} 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-2016-041.html - Submitted to Phys. Lett. BInternational audienceA search for CP violation in D±→η′π± and D±s→η′π± decays is performed using proton-proton collision data, corresponding to an integrated luminosity of 3 fb−1, recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The measured CP-violating charge asymmetries are ACP(D±→η′π±)=(−0.61±0.72±0.55±0.12)% and ACP(D±s→η′π±)=(−0.82±0.36±0.24±0.27)%, where the first uncertainties are statistical, the second systematic, and the third are the uncertainties on the ACP(D±→K0Sπ±) and ACP(D±s→ϕπ±) measurements used for calibration. The results represent the most precise measurements of these asymmetries to date

Observation of ηc(2S)→ppˉ\eta_{c}(2S) \to p \bar p and search for X(3872)→ppˉX(3872) \to p \bar p decays

The first observation of the decay $\eta_{c}(2S) \to p \bar p$ is reported using proton-proton collision data corresponding to an integrated luminosity of $3.0\rm \, fb^{-1}$ recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The $\eta_{c}(2S)$ resonance is produced in the decay $B^{+} \to [c\bar c] K^{+}$. The product of branching fractions normalised to that for the $J/\psi$ intermediate state, ${\cal R}_{\eta_{c}(2S)}$, is measured to be \begin{align*} {\cal R}_{\eta_{c}(2S)}\equiv\frac{{\mathcal B}(B^{+} \to \eta_{c}(2S) K^{+}) \times {\mathcal B}(\eta_{c}(2S) \to p \bar p)}{{\mathcal B}(B^{+} \to J/\psi K^{+}) \times {\mathcal B}(J/\psi\to p \bar p)} =~& (1.58 \pm 0.33 \pm 0.09)\times 10^{-2}, \end{align*} where the first uncertainty is statistical and the second systematic. No signals for the decays $B^{+} \to X(3872) (\to p \bar p) K^{+}$ and $B^{+} \to \psi(3770) (\to p \bar p) K^{+}$ are seen, and the 95\% confidence level upper limits on their relative branching ratios are % found to be ${\cal R}_{X(3872)}<0.25\times10^{-2}$ and ${\cal R}_{\psi(3770))}<0.10$. In addition, the mass differences between the $\eta_{c}(1S)$ and the $J/\psi$ states, between the $\eta_{c}(2S)$ and the $\psi(2S)$ states, and the natural width of the $\eta_{c}(1S)$ are measured as \begin{align*} M_{J/\psi} - M_{\eta_{c}(1S)} =~& 110.2 \pm 0.5 \pm 0.9 \rm \, MeV, M_{\psi(2S)} -M_{\eta_{c}(2S)} =~ & 52.5 \pm 1.7 \pm 0.6 \rm \, MeV, \Gamma_{\eta_{c}(1S)} =~& 34.0 \pm 1.9 \pm 1.3 \rm \, MeV. \end{align*}Comment: 16 pages, 2 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-2016-016.htm

Measurement of B0B^0, Bs0B^0_s, B+B^+ and Λb0\Lambda^0_b production asymmetries in 7 and 8 TeV proton-proton collisions

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-2016-062.html - Submitted to Phys. Lett. B.International audienceThe B0, B0s, B+ and Λ0b hadron production asymmetries are measured using a data sample corresponding to an integrated luminosity of 3.0 fb−1, collected by the LHCb experiment in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. The measurements are performed as a function of transverse momentum and rapidity of the b hadrons within the LHCb detector acceptance. The overall production asymmetries, integrated over transverse momentum and rapidity, are also determined

Search for CPCP violation in the phase space of D0→π+π−π+π−D^0\rightarrow\pi^+\pi^-\pi^+\pi^- decays

A search for time-integrated $CP$ violation in the Cabibbo-suppressed decay \mbox{D^0\rightarrow\pi^+\pi^-\pi^+\pi^-} is performed using an unbinned, model-independent technique known as the energy test. This is the first application of the energy test in four-body decays. The search is performed for $P$-even $CP$ asymmetries and, for the first time, is extended to probe the $P$-odd case. Using proton-proton collision data corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector at centre-of-mass energies of $\sqrt{s}=$7 TeV and 8 TeV, the world's best sensitivity to $CP$ violation in this decay is obtained. The data are found to be consistent with the hypothesis of $CP$ symmetry with a $p$-value of $(4.6\pm0.5)\%$ in the $P$-even case, and marginally consistent with a $p$-value of $(0.6\pm0.2)\%$ in the $P$-odd case, corresponding to a significance for $CP$ non-conservation of 2.7 standard deviations.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-2016-044.htm

First observation of forward Z→bbˉZ \rightarrow b \bar{b} production in pppp collisions at s=8\sqrt{s}=8 TeV

The decay Z→bb¯ is reconstructed in pp collision data, corresponding to 2 fb −1 of integrated luminosity, collected by the LHCb experiment at a centre-of-mass energy of s=8 TeV. The product of the Z production cross-section and the Z→bb¯ branching fraction is measured for candidates in the fiducial region defined by two particle-level b -quark jets with pseudorapidities in the range 2.220 GeV and dijet invariant mass in the range 4520$GeV and dijet invariant mass in the range$45 < m_{jj} < 165$GeV. From a signal yield of$5462 \pm 763$$Z \rightarrow b \bar{b}$events, where the uncertainty is statistical, a production cross-section times branching fraction of$332 \pm 46 \pm 59$pb is obtained, where the first uncertainty is statistical and the second systematic. The measured significance of the signal yield is 6.0 standard deviations. This measurement represents the first observation of the$Z \rightarrow b \bar{b}$production in the forward region of$pp$ collisions