Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Measurement and QCD analysis of double-differential inclusive jet cross sections in proton-proton collisions at root s=13 TeV

A search for flavor-changing neutral current interactions of the top quark (t) and the Higgs boson (H) is presented. The search is based on a data sample corresponding to an integrated luminosity of 137 fb(-1) recorded by the CMS experiment at the LHC in proton-proton collisions at root s = 13TeV. Events containing exactly one lepton (muon or electron) and at least three jets, among which at least two are identified as originating from the hadronization of a bottom quark, are analyzed. A set of deep neural networks is used for kinematic event reconstruction, while boosted decision trees distinguish the signal from the background events. No significant excess over the background predictions is observed, and upper limits on the signal production cross sections are extracted. These limits are interpreted in terms of top quark decay branching fractions (B) to the Higgs boson and an up (u) or a charm quark (c). Assuming one nonvanishing extra coupling at a time, the observed (expected) upper limits at 95% confidence level are B(t -> Hu) Hc) < 0.094 (0.086)%

Proton reconstruction with the CMS-TOTEM Precision Proton Spectrometer

The Precision Proton Spectrometer (PPS) of the CMS and TOTEM experiments collected 107.7 fb 1 in proton-proton (pp) collisions at the LHC at 13 TeV(Run 2). This paper describes the key features of the PPS alignment and optics calibrations, the proton reconstruction procedure, as well as the detector efficiency and the performance of the PPS simulation. The reconstruction and simulation are validated using a sample of (semi)exclusive dilepton events. The performance of PPS has proven the feasibility of continuously operating a near-beam proton spectrometer at a high luminosity hadron collider

Measurement of the Drell-Yan forward-backward asymmetry at high dilepton masses in proton-proton collisions at root s=13 TeV

A measurement of the forward-backward asymmetry of pairs of oppositely charged leptons (dimuons and dielectrons) produced by the Drell-Yan process in proton-proton collisions is presented. The data sample corresponds to an integrated luminosity of 138 fb(-1) collected with the CMS detector at the LHC at a center-of-mass energy of 13 TeV. The asymmetry is measured as a function of lepton pair mass for masses larger than 170 GeV and compared with standard model predictions. An inclusive measurement across both channels and the full mass range yields an asymmetry of 0.612 +/- 0.005 (stat) +/- 0.007 (syst). As a test of lepton flavor universality, the difference between the dimuon and dielectron asymmetries is measured as well. No statistically significant deviations from standard model predictions are observed. The measurements are used to set limits on the presence of additional gauge bosons. For a Z' boson in the sequential standard model the observed (expected) 95% confidence level lower limit on the Z' mass is 4.4 TeV (3.7 TeV)

Search for new physics in high-mass diphoton events from proton-proton collisions at √s = 13 TeV

Results are presented from a search for new physics in high-mass diphoton events from proton-proton collisions at sqrt(s) = 13 TeV. The data set was collected in 2016–2018 with the CMS detector at the LHC and corresponds to an integrated luminosity of 138 fb−1 . Events with a diphoton invariant mass greater than 500 GeV are considered. Two diferent techniques are used to predict the standard model backgrounds: parametric fts to the smoothly-falling background and a frst-principles calculation of the standard model diphoton spectrum at next-to-next-to-leading order in perturbative quantum chromodynamics calculations. The frst technique is sensitive to resonant excesses while the second technique can identify broad diferences in the invariant mass shape. The data are used to constrain the production of heavy Higgs bosons, Randall-Sundrum gravitons, the large extra dimensions model of Arkani-Hamed, Dimopoulos, and Dvali (ADD), and the continuum clockwork mechanism. No statistically signifcant excess is observed. The present results are the strongest limits to date on ADD extra dimensions and RS gravitons with a coupling parameter greater than 0.1

Search for Z′ bosons decaying to pairs of heavy Majorana neutrinos in proton-proton collisions at √s = 13 TeV

A search for the production of pairs of heavy Majorana neutrinos (Nl ) from the decays of Z ′ bosons is performed using the CMS detector at the LHC. The data were collected in proton-proton collisions at a center-of-mass energy of √ s = 13 TeV, with an integrated luminosity of 138 fb−1 . The signature for the search is an excess in the invariant mass distribution of the fnal-state objects, two same-favor leptons (e or μ) and at least two jets. No signifcant excess of events beyond the expected background is observed. Upper limits at 95% confdence level are set on the product of the Z ′ production cross section and its branching fraction to a pair of Nl , as functions of Nl and Z ′ boson masses (mNl and mZ ′, respectively) for mZ ′ from 0.4 to 4.6 TeV and mNl from 0.1 TeV to mZ ′/2. In the theoretical framework of a left-right symmetric model, exclusion bounds in the mNl -mZ ′ plane are presented in both the electron and muon channels. The observed upper limit on mZ ′ reaches up to 4.42 TeV. These are the most restrictive limits to date on the mass of Nl as a function of the Z ′ boson mass

Search for Higgs Boson Decay to a Charm Quark-Antiquark Pair in Proton-Proton Collisions at √s=13 TeV

A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, H→c⁢ ̄ c , produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at √s=13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138 fb−1. Novel charm jet identification and analysis methods using machine learning techniques are employed. The analysis is validated by searching for Z→c⁢ ̄ c in V⁢Z events, leading to its first observation at a hadron collider with a significance of 5.7 standard deviations. The observed (expected) upper limit on σ⁡(V⁢H)⁢B⁡(H→c⁢ ̄ c ) is 0.94 (0.50+0.22 −0.15)pb at 95% confidence level (C.L.), corresponding to 14 (7.6+3.4 −2.3) times the standard model prediction. For the Higgs-charm Yukawa coupling modifier, κc, the observed (expected) 95% C.L. interval is 1.1&lt;|κc|&lt;5.5 (|κc|&lt;3.4), the most stringent constraint to date

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Worldwide trends in underweight and obesity from 1990 to 2022 : a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

A list of authors and their affiliations appears online. A supplementary appendix is herewith attached.Background: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity.peer-reviewe