Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Transverse momentum and pseudorapidity distributions of charged hadrons in pp collisions at (s)\sqrt(s) = 0.9 and 2.36 TeV

Measurements of inclusive charged-hadron transverse-momentum and pseudorapidity distributions are presented for proton-proton collisions at sqrt(s) = 0.9 and 2.36 TeV. The data were collected with the CMS detector during the LHC commissioning in December 2009. For non-single-diffractive interactions, the average charged-hadron transverse momentum is measured to be 0.46 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 0.9 TeV and 0.50 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 2.36 TeV, for pseudorapidities between -2.4 and +2.4. At these energies, the measured pseudorapidity densities in the central region, dN(charged)/d(eta) for |eta| < 0.5, are 3.48 +/- 0.02 (stat.) +/- 0.13 (syst.) and 4.47 +/- 0.04 (stat.) +/- 0.16 (syst.), respectively. The results at 0.9 TeV are in agreement with previous measurements and confirm the expectation of near equal hadron production in p-pbar and pp collisions. The results at 2.36 TeV represent the highest-energy measurements at a particle collider to date

Measurement of the lepton charge asymmetry in inclusive WW production in pp collisions at s=7\sqrt{s} = 7 TeV

A measurement of the lepton charge asymmetry in inclusive pp to WX production at sqrt(s)= 7 TeV is presented based on data recorded by the CMS detector at the LHC and corresponding to an integrated luminosity of 36 inverse picobarns. This high precision measurement of the lepton charge asymmetry, performed in both the W to e nu and W to mu nu channels, provides new insights into parton distribution functions.A measurement of the lepton charge asymmetry in inclusive pp to WX production at sqrt(s)= 7 TeV is presented based on data recorded by the CMS detector at the LHC and corresponding to an integrated luminosity of 36 inverse picobarns. This high precision measurement of the lepton charge asymmetry, performed in both the W to e nu and W to mu nu channels, provides new insights into parton distribution functions.A measurement of the lepton charge asymmetry in inclusive pp to WX production at sqrt(s)= 7 TeV is presented based on data recorded by the CMS detector at the LHC and corresponding to an integrated luminosity of 36 inverse picobarns. This high precision measurement of the lepton charge asymmetry, performed in both the W to e nu and W to mu nu channels, provides new insights into parton distribution functions