199 research outputs found
Identifying potential causal effects of age at menarche: A Mendelian randomization phenome-wide association study
Background: Age at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner. Methods: We conducted a Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n = 181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations. Results: Of the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null. Conclusions: The genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available
Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease
Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5Ă10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD
Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts
Background Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants
that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants
would predict COPD and associated phenotypes.
Methods We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and
FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine
cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1
<80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking
pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area
under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that
reflect parenchymal and airway pathology, and patterns of reduced lung growth.
Findings The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81
[95% CI 1·74â1·88] and non-European (1·42 [1·34â1·51]) populations. Compared with the first decile, the tenth decile
of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56â9·72) in European ancestry and
4·83 (3·45â6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described
genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed
improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79â0·81]
vs 0·76 [0·75â0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area
percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive
emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern.
Interpretation A risk score comprised of genetic variants can identify a small subset of individuals at markedly
increased risk for moderate-to-severe COPD, emphysema subtyp
Study of the production of and hadrons in collisions and first measurement of the branching fraction
The product of the () differential production
cross-section and the branching fraction of the decay () is
measured as a function of the beauty hadron transverse momentum, ,
and rapidity, . The kinematic region of the measurements is and . The measurements use a data sample
corresponding to an integrated luminosity of collected by the
LHCb detector in collisions at centre-of-mass energies in 2011 and in 2012. Based on previous LHCb
results of the fragmentation fraction ratio, , the
branching fraction of the decay 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 , and the
fourth is due to the knowledge of . The sum of the
asymmetries in the production and decay between and
is also measured as a function of and .
The previously published branching fraction of , relative to that of , is updated.
The branching fractions of 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
Evidence for the strangeness-changing weak decay
Using a collision data sample corresponding to an integrated luminosity
of 3.0~fb, collected by the LHCb detector, we present the first search
for the strangeness-changing weak decay . No
hadron decay of this type has been seen before. A signal for this decay,
corresponding to a significance of 3.2 standard deviations, is reported. The
relative rate is measured to be
, where and
are the and fragmentation
fractions, and is the branching
fraction. Assuming is bounded between 0.1 and
0.3, the branching fraction would lie
in the range from to .Comment: 7 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-2015-047.htm
flavour tagging using charm decays at the LHCb experiment
An algorithm is described for tagging the flavour content at production of
neutral mesons in the LHCb experiment. The algorithm exploits the
correlation of the flavour of a meson with the charge of a reconstructed
secondary charm hadron from the decay of the other 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 and using of data collected by the LHCb
experiment at centre-of-mass energies of and
. Its tagging power on these samples of
decays is .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
Measurements of long-range near-side angular correlations in TeV proton-lead collisions in the forward region
Two-particle angular correlations are studied in proton-lead collisions at a
nucleon-nucleon centre-of-mass energy of TeV, collected
with the LHCb detector at the LHC. The analysis is based on data recorded in
two beam configurations, in which either the direction of the proton or that of
the lead ion is analysed. The correlations are measured in the laboratory
system as a function of relative pseudorapidity, , and relative
azimuthal angle, , for events in different classes of event
activity and for different bins of particle transverse momentum. In
high-activity events a long-range correlation on the near side, , is observed in the pseudorapidity range . This
measurement of long-range correlations on the near side in proton-lead
collisions extends previous observations into the forward region up to
. The correlation increases with growing event activity and is found
to be more pronounced in the direction of the lead beam. However, the
correlation in the direction of the lead and proton beams are found to be
compatible when comparing events with similar absolute activity in the
direction analysed.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-2015-040.htm
Identification of beauty and charm quark jets at LHCb
Identification of jets originating from beauty and charm quarks is important
for measuring Standard Model processes and for searching for new physics. The
performance of algorithms developed to select - and -quark jets is
measured using data recorded by LHCb from proton-proton collisions at
TeV in 2011 and at TeV in 2012. The efficiency for
identifying a jet is about 65%(25%) with a probability for
misidentifying a light-parton jet of 0.3% for jets with transverse momentum
GeV and pseudorapidity . The dependence of
the performance on the and of the jet is also measured
Prompt charm production in pp collisions at √<span style="text-decoration:overline">s</span>=7 TeV
Charm production at the LHC in pp collisions at sâ=7 TeV is studied with the LHCb detector. The decays D0âKâÏ+, D+âKâÏ+Ï+, Dâ+âD0(KâÏ+)Ï+, D+sâÏ(KâK+)Ï+, Î+câpKâÏ+, and their charge conjugates are analysed in a data set corresponding to an integrated luminosity of 15 nbâ1. Differential cross-sections dÏ/dpT are measured for prompt production of the five charmed hadron species in bins of transverse momentum and rapidity in the region 0<pT<8 GeV/c and 2.0<y<4.5. Theoretical predictions are compared to the measured differential cross-sections. The integrated cross-sections of the charm hadrons are computed in the above pT-y range, and their ratios are reported. A combination of the five integrated cross-section measurements gives
Ï(ccÂŻ)pT<8 GeV/c,2.0<y<4.5=1419±12(stat)±116(syst)±65(frag) Όb,
where the uncertainties are statistical, systematic, and due to the fragmentation functions
- âŠ