Ancestry-specific associations identified in genome-wide combined-phenotype study of red blood cell traits emphasize benefits of diversity in genomics

Background: Quantitative red blood cell (RBC) traits are highly polygenic clinically relevant traits, with approximately 500 reported GWAS loci. The majority of RBC trait GWAS have been performed in European- or East Asian-ancestry populations, despite evidence that rare or ancestry-specific variation contributes substantially to RBC trait heritability. Recently developed combined-phenotype methods which leverage genetic trait correlation to improve statistical power have not yet been applied to these traits. Here we leveraged correlation of seven quantitative RBC traits in performing a combined-phenotype analysis in a multi-ethnic study population. Results: We used the adaptive sum of powered scores (aSPU) test to assess combined-phenotype associations between ~ 21 million SNPs and seven RBC traits in a multi-ethnic population (maximum n = 67,885 participants; 24% African American, 30% Hispanic/Latino, and 43% European American; 76% female). Thirty-nine loci in our multi-ethnic population contained at least one significant association signal (p 5%) across all ancestral populations. Nineteen additional independent association signals were identified at seven known loci (HFE, KIT, HBS1L/MYB, CITED2/FILNC1, ABO, HBA1/2, and PLIN4/5). For example, the HBA1/2 locus contained 14 conditionally independent association signals, 11 of which were previously unreported and are specific to African and Amerindian ancestries. One variant in this region was common in all ancestries, but exhibited a narrower LD block in African Americans than European Americans or Hispanics/Latinos. GTEx eQTL analysis of all independent lead SNPs yielded 31 significant associations in relevant tissues, over half of which were not at the gene immediately proximal to the lead SNP. Conclusion: This work identified seven loci containing multiple independent association signals for RBC traits using a combined-phenotype approach, which may improve discovery in genetically correlated traits. Highly complex genetic architecture at the HBA1/2 locus was only revealed by the inclusion of African Americans and Hispanics/Latinos, underscoring the continued importance of expanding large GWAS to include ancestrally diverse populations. © 2020 The Author(s)

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Model-independent search for CP violation in D0→K−K+π−π+ and D0→π−π+π+π− decays

A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states K−K+π−π+ and π−π+π+π− is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fb−1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the K−K+π−π+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the π−π+π+π− final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity

Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays

Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of prime importance in probing new physics. Here 7421 +/- 105 signal events from the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A time-dependent fit to the data yields a value of phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201

Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓

A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions at √s=7  TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101  TeV/c2 and MLQ(B0→e±μ∓)>126  TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds

Absolute luminosity measurements with the LHCb detector at the LHC

Absolute luminosity measurements are of general interest for colliding-beam experiments at storage rings. These measurements are necessary to determine the absolute cross-sections of reaction processes and are valuable to quantify the performance of the accelerator. Using data taken in 2010, LHCb has applied two methods to determine the absolute scale of its luminosity measurements for proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In addition to the classic "van der Meer scan" method a novel technique has been developed which makes use of direct imaging of the individual beams using beam-gas and beam-beam interactions. This beam imaging method is made possible by the high resolution of the LHCb vertex detector and the close proximity of the detector to the beams, and allows beam parameters such as positions, angles and widths to be determined. The results of the two methods have comparable precision and are in good agreement. Combining the two methods, an overall precision of 3.5% in the absolute luminosity determination is reached. The techniques used to transport the absolute luminosity calibration to the full 2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6, 9 and 10 and corresponding explanation in the tex

Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) and the direct CP asymmetry in B0 -> K*0 gamma

The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma and Bs0 phi gamma has been measured using an integrated luminosity of 1.0 fb-1 of pp collision data collected by the LHCb experiment at a centre-of-mass energy of sqrt(s)=7 TeV. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.23 +/- 0.06(stat.) +/- 0.04(syst.) +/- 0.10(fs/fd), where the first uncertainty is statistical, the second is the experimental systematic uncertainty and the third is associated with the ratio of fragmentation fractions fs/fd. Using the world average value for BR(B0 -> K*0 gamma), the branching fraction BR(Bs0 -> phi gamma) is measured to be (3.5 +/- 0.4) x 10^{-5}. The direct CP asymmetry in B0 -> K*0 gamma decays has also been measured with the same data and found to be A(CP)(B0 -> K*0 gamma) = (0.8 +/- 1.7(stat.) +/- 0.9(syst.))%. Both measurements are the most precise to date and are in agreement with the previous experimental results and theoretical expectations.Comment: 21 pages, 3 figues, 4 table

Absolute luminosity measurements with the LHCb detector at the LHC

Absolute luminosity measurements are of general interest for colliding-beam experiments at storage rings. These measurements are necessary to determine the absolute cross-sections of reaction processes and are valuable to quantify the performance of the accelerator. Using data taken in 2010, LHCb has applied two methods to determine the absolute scale of its luminosity measurements for proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In addition to the classic "van der Meer scan" method a novel technique has been developed which makes use of direct imaging of the individual beams using beam-gas and beam-beam interactions. This beam imaging method is made possible by the high resolution of the LHCb vertex detector and the close proximity of the detector to the beams, and allows beam parameters such as positions, angles and widths to be determined. The results of the two methods have comparable precision and are in good agreement. Combining the two methods, an overall precision of 3.5% in the absolute luminosity determination is reached. The techniques used to transport the absolute luminosity calibration to the full 2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6, 9 and 10 and corresponding explanation in the tex

Absolute luminosity measurements with the LHCb detector at the LHC

Absolute luminosity measurements are of general interest for colliding-beam experiments at storage rings. These measurements are necessary to determine the absolute cross-sections of reaction processes and are valuable to quantify the performance of the accelerator. Using data taken in 2010, LHCb has applied two methods to determine the absolute scale of its luminosity measurements for proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In addition to the classic "van der Meer scan" method a novel technique has been developed which makes use of direct imaging of the individual beams using beam-gas and beam-beam interactions. This beam imaging method is made possible by the high resolution of the LHCb vertex detector and the close proximity of the detector to the beams, and allows beam parameters such as positions, angles and widths to be determined. The results of the two methods have comparable precision and are in good agreement. Combining the two methods, an overall precision of 3.5% in the absolute luminosity determination is reached. The techniques used to transport the absolute luminosity calibration to the full 2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6, 9 and 10 and corresponding explanation in the tex

Study of the production of Λb0\Lambda_b^0 and B‾0\overline{B}^0 hadrons in pppp collisions and first measurement of the Λb0→J/ψpK−\Lambda_b^0\rightarrow J/\psi pK^- branching fraction

The product of the $\Lambda_b^0$ ($\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ ($\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\rm T}<20~{\rm GeV}/c$ and $2.0<y<4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\sqrt{s}=7~{\rm TeV}$ in 2011 and $\sqrt{s}=8~{\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\Lambda_B^0}/f_d$, the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ is measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4}, \end{equation*} where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay $\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$, and the fourth is due to the knowledge of $f_{\Lambda_b^0}/f_d$. The sum of the asymmetries in the production and decay between $\Lambda_b^0$ and $\overline{\Lambda}_b^0$ is also measured as a function of $p_{\rm T}$ and $y$. The previously published branching fraction of $\Lambda_b^0\rightarrow J/\psi p\pi^-$, relative to that of $\Lambda_b^0\rightarrow J/\psi pK^-$, is updated. The branching fractions of $\Lambda_b^0\rightarrow P_c^+(\rightarrow J/\psi p)K^-$ are determined.Comment: 29 pages, 19figures. 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-2015-032.htm