881 research outputs found
New insights from genetic studies of eczema
Genome-wide association studies (GWAS) provided fundamental insight into the genetic determinants of complex allergic diseases. For eczema, 58 susceptibility loci were reported. Protein-changing variants were associated with eczema at genome-wide significance at 12 loci. The majority of risk variants were, however, located in non-coding, regulatory regions of the genome. Prioritized target genes were enriched in pathways of the immune response and of epithelial barrier function. Interestingly, a large overlap in the genetic architecture underlying different allergic diseases was identified pointing to common pathomechanisms for eczema, asthma, hay fever, and food allergy. Here, we review the most recent findings from GWAS for eczema including the role of rare variants and genetic heterogeneity in ethnically diverse populations. In addition, we provide an overview of genes underlying Mendelian disorders featuring eczematous skin inflammation
Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder
Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity
DNA sequence level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders
Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes
Observation of an Excited Bc+ State
Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+Ï+Ï- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bcâ(2S31)+ state reconstructed without the low-energy photon from the Bcâ(1S31)+âBc+Îł decay following Bcâ(2S31)+âBcâ(1S31)+Ï+Ï-. A second state is seen with a global (local) statistical significance of 2.2Ï (3.2Ï) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date
Measurement of the lifetime
Using a data set corresponding to an integrated luminosity of ,
collected by the LHCb experiment in collisions at centre-of-mass energies
of 7 and 8 TeV, the effective lifetime in the
decay mode, , is measured to be ps. Assuming
conservation, corresponds to the lifetime of the light
mass eigenstate. This is the first measurement of the effective
lifetime in this decay mode.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-2016-017.htm
Study of charmonium production in b -hadron decays and first evidence for the decay Bs0
Using decays to Ï-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 fbâ1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. Denoting byBC ⥠B(b â C X) Ă B(C â ÏÏ) the inclusive branching fraction of a b hadron to a charmonium state C that decays into a pair of Ï mesons, ratios RC1C2 ⥠BC1 /BC2 are determined as RÏc0ηc(1S) = 0.147 ± 0.023 ± 0.011, RÏc1ηc(1S) =0.073 ± 0.016 ± 0.006, RÏc2ηc(1S) = 0.081 ± 0.013 ± 0.005,RÏc1 Ïc0 = 0.50 ± 0.11 ± 0.01, RÏc2 Ïc0 = 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 Ïc2(2P) states are obtained as RX(3872)Ïc1 < 0.34, RX(3915)Ïc0 < 0.12 andRÏc2(2P)Ïc2 < 0.16. Differential cross-sections as a function of transverse momentum are measured for the ηc(1S) andÏc states. The branching fraction of the decay B0s â ÏÏÏ is measured for the first time, B(B0s â ÏÏÏ) = (2.15±0.54±0.28±0.21B)Ă10â6. Here the third uncertainty is due to the branching fraction of the decay B0s â ÏÏ, which is used for normalization. No evidence for intermediate resonances is seen. A preferentially transverse Ï polarization is observed.The measurements allow the determination of the ratio of the branching fractions for the ηc(1S) decays to ÏÏ and p p asB(ηc(1S)â ÏÏ)/B(ηc(1S)â p p) = 1.79 ± 0.14 ± 0.32
Study of J /Ï production in Jets
The production of J/Ï mesons in jets is studied in the forward region of proton-proton collisions using data collected with the LHCb detector at a center-of-mass energy of 13 TeV. The fraction of the jet transverse momentum carried by the J/Ï meson, z(J/Ï)âĄpT(J/Ï)/pT(jet), is measured using jets with pT(jet)>20 GeV in the pseudorapidity range 2.5<η(jet)<4.0. The observed z(J/Ï)distribution for J/Ï mesons produced in b-hadron decays is consistent with expectations. However, the results for prompt J/Ï production do not agree with predictions based on fixed-order nonrelativistic QCD. This is the first measurement of the pT fraction carried by prompt J/Ï mesons in jets at any experiment
Model-independent evidence for contributions to decays
The data sample of decays acquired with the
LHCb detector from 7 and 8~TeV collisions, corresponding to an integrated
luminosity of 3 fb, is inspected for the presence of or
contributions with minimal assumptions about
contributions. It is demonstrated at more than 9 standard deviations that
decays cannot be described with
contributions alone, and that contributions play a dominant role in
this incompatibility. These model-independent results support the previously
obtained model-dependent evidence for charmonium-pentaquark
states in the same data sample.Comment: 21 pages, 12 figures (including the supplemental section added at the
end
Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at âs=7 TeV
Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected
by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the
form of an enhancement of pairs of like-sign charged pions with small four-momentum
difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source
is investigated, determining both the correlation radius and the chaoticity parameter. The
measured correlation radius is found to increase as a function of increasing charged-particle
multiplicity, while the chaoticity parameter is seen to decreas
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