175 research outputs found
Genome-Wide Interaction and Pathway Association Studies for Body Mass Index
Objective: We investigated gene interactions (epistasis) for body mass index (BMI) in a European-American adult female cohort via genome-wide interaction analyses (GWIA) and pathway association analyses.Methods: Genome-wide pairwise interaction analyses were carried out for BMI in 493 extremely obese cases (BMI > 35 kg/m2) and 537 never-overweight controls (BMI < 25 kg/m2). To further validate the results, specific SNPs were selected based on the GWIA results for haplotype-based association studies. Pathway-based association analyses were performed using a modified Gene Set Enrichment Algorithm (GSEA) (GenGen program) to further explore BMI-related pathways using our genome wide association study (GWAS) data set, GIANT, ENGAGE, and DIAGRAM Consortia.Results: The EXOC4-1q23.1 interaction was associated with BMI, with the most significant epistasis between rs7800006 and rs10797020 (P = 2.63 × 10-11). In the pathway-based association analysis, Tob1 pathway showed the most significant association with BMI (empirical P < 0.001, FDR = 0.044, FWER = 0.040). These findings were further validated in different populations.Conclusion: Genome-wide pairwise SNP-SNP interaction and pathway analyses suggest that EXOC4 and TOB1-related pathways may contribute to the development of obesity
FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs
<p>Abstract</p> <p>Background</p> <p>FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs) in FTO with body mass index (BMI) and obesity, particularly rs1421085, rs17817449, and rs9939609.</p> <p>Methods</p> <p>We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m<sup>2 </sup>and lifetime BMI greater than 40 kg/m<sup>2</sup>, and 544 controls who were currently normal weight (BMI<25 kg/m<sup>2</sup>) and had never been overweight during their lifetimes.</p> <p>Results</p> <p>We detected highly significant associations of obesity with alleles in all three SNPs (p < 10<sup>-9</sup>). The strongest association was with rs1421085 (p = 3.04 × 10<sup>-10</sup>, OR = 1.75, CI = 1.47–2.08). A subset of 99 cases had extremely discordant sisters with BMI<25 kg/m<sup>2</sup>. The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 × 10<sup>-4</sup>).</p> <p>Conclusion</p> <p>These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.</p
A Genome-Wide Association Study on Obesity and Obesity-Related Traits
Large-scale genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI), but few studies focused on obesity as a binary trait. Here we report the results of a GWAS and candidate SNP genotyping study of obesity, including extremely obese cases and never overweight controls as well as families segregating extreme obesity and thinness. We first performed a GWAS on 520 cases (BMI>35 kg/m2) and 540 control subjects (BMI<25 kg/m2), on measures of obesity and obesity-related traits. We subsequently followed up obesity-associated signals by genotyping the top ∼500 SNPs from GWAS in the combined sample of cases, controls and family members totaling 2,256 individuals. For the binary trait of obesity, we found 16 genome-wide significant signals within the FTO gene (strongest signal at rs17817449, P = 2.5×10−12). We next examined obesity-related quantitative traits (such as total body weight, waist circumference and waist to hip ratio), and detected genome-wide significant signals between waist to hip ratio and NRXN3 (rs11624704, P = 2.67×10−9), previously associated with body weight and fat distribution. Our study demonstrated how a relatively small sample ascertained through extreme phenotypes can detect genuine associations in a GWAS
Search for non-relativistic Magnetic Monopoles with IceCube
The IceCube Neutrino Observatory is a large Cherenkov detector instrumenting
of Antarctic ice. The detector can be used to search for
signatures of particle physics beyond the Standard Model. Here, we describe the
search for non-relativistic, magnetic monopoles as remnants of the GUT (Grand
Unified Theory) era shortly after the Big Bang. These monopoles may catalyze
the decay of nucleons via the Rubakov-Callan effect with a cross section
suggested to be in the range of to
. In IceCube, the Cherenkov light from nucleon decays
along the monopole trajectory would produce a characteristic hit pattern. This
paper presents the results of an analysis of first data taken from May 2011
until May 2012 with a dedicated slow-particle trigger for DeepCore, a
subdetector of IceCube. A second analysis provides better sensitivity for the
brightest non-relativistic monopoles using data taken from May 2009 until May
2010. In both analyses no monopole signal was observed. For catalysis cross
sections of the flux of non-relativistic
GUT monopoles is constrained up to a level of at a 90% confidence level,
which is three orders of magnitude below the Parker bound. The limits assume a
dominant decay of the proton into a positron and a neutral pion. These results
improve the current best experimental limits by one to two orders of magnitude,
for a wide range of assumed speeds and catalysis cross sections.Comment: 20 pages, 20 figure
The IceCube Neutrino Observatory - Contributions to ICRC 2015 Part II: Atmospheric and Astrophysical Diffuse Neutrino Searches of All Flavors
Papers on atmospheric and astrophysical diffuse neutrino searches of all
flavors submitted to the 34th International Cosmic Ray Conference (ICRC 2015,
The Hague) by the IceCube Collaboration.Comment: 66 pages, 36 figures, Papers submitted to the 34th International
Cosmic Ray Conference, The Hague 2015, v2 has a corrected author lis
A combined maximum-likelihood analysis of the high-energy astrophysical neutrino flux measured with IceCube
Evidence for an extraterrestrial flux of high-energy neutrinos has now been
found in multiple searches with the IceCube detector. The first solid evidence
was provided by a search for neutrino events with deposited energies
TeV and interaction vertices inside the instrumented volume. Recent
analyses suggest that the extraterrestrial flux extends to lower energies and
is also visible with throughgoing, -induced tracks from the Northern
hemisphere. Here, we combine the results from six different IceCube searches
for astrophysical neutrinos in a maximum-likelihood analysis. The combined
event sample features high-statistics samples of shower-like and track-like
events. The data are fit in up to three observables: energy, zenith angle and
event topology. Assuming the astrophysical neutrino flux to be isotropic and to
consist of equal flavors at Earth, the all-flavor spectrum with neutrino
energies between 25 TeV and 2.8 PeV is well described by an unbroken power law
with best-fit spectral index and a flux at 100 TeV of
.
Under the same assumptions, an unbroken power law with index is disfavored
with a significance of 3.8 () with respect to the best
fit. This significance is reduced to 2.1 () if instead we
compare the best fit to a spectrum with index that has an exponential
cut-off at high energies. Allowing the electron neutrino flux to deviate from
the other two flavors, we find a fraction of at Earth.
The sole production of electron neutrinos, which would be characteristic of
neutron-decay dominated sources, is rejected with a significance of 3.6
().Comment: 16 pages, 10 figures; accepted for publication in The Astrophysical
Journal; updated one referenc
Characterization of the Atmospheric Muon Flux in IceCube
Muons produced in atmospheric cosmic ray showers account for the by far
dominant part of the event yield in large-volume underground particle
detectors. The IceCube detector, with an instrumented volume of about a cubic
kilometer, has the potential to conduct unique investigations on atmospheric
muons by exploiting the large collection area and the possibility to track
particles over a long distance. Through detailed reconstruction of energy
deposition along the tracks, the characteristics of muon bundles can be
quantified, and individual particles of exceptionally high energy identified.
The data can then be used to constrain the cosmic ray primary flux and the
contribution to atmospheric lepton fluxes from prompt decays of short-lived
hadrons.
In this paper, techniques for the extraction of physical measurements from
atmospheric muon events are described and first results are presented. The
multiplicity spectrum of TeV muons in cosmic ray air showers for primaries in
the energy range from the knee to the ankle is derived and found to be
consistent with recent results from surface detectors. The single muon energy
spectrum is determined up to PeV energies and shows a clear indication for the
emergence of a distinct spectral component from prompt decays of short-lived
hadrons. The magnitude of the prompt flux, which should include a substantial
contribution from light vector meson di-muon decays, is consistent with current
theoretical predictions.Comment: 36 pages, 39 figure
The IceCube Neutrino Observatory - Contributions to ICRC 2015 Part III: Cosmic Rays
Papers on cosmic rays submitted to the 34th International Cosmic Ray
Conference (ICRC 2015, The Hague) by the IceCube Collaboration.Comment: 83 pages, 52 figues, Papers submitted to the 34th International
Cosmic Ray Conference, The Hague 2015, v2 has a corrected author lis
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