316 research outputs found
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Targeted Resequencing of the Coding Sequence of 38 Genes Near Breast Cancer GWAS Loci in a Large Case-Control Study.
BACKGROUND: Genes regulated by breast cancer risk alleles identified through genome-wide association studies (GWAS) may harbor rare coding risk alleles. METHODS: We sequenced the coding regions for 38 genes within 500 kb of 38 lead GWAS SNPs in 13,538 breast cancer cases and 5,518 controls. RESULTS: Truncating variants in these genes were rare, and were not associated with breast cancer risk. Burden testing of rare missense variants highlighted 5 genes with some suggestion of an association with breast cancer, although none met the multiple testing thresholds: MKL1, FTO, NEK10, MDM4, and COX11. Six common alleles in COX11, MAP3K1 (two), and NEK10 (three) were associated at the P < 0.0001 significance level, but these likely reflect linkage disequilibrium with causal regulatory variants. CONCLUSIONS: There was no evidence that rare coding variants in these genes confer substantial breast cancer risks. However, more modest effect sizes could not be ruled out. IMPACT: We tested the hypothesis that rare variants in 38 genes near breast cancer GWAS loci may mediate risk. These variants do not appear to play a major role in breast cancer heritability
Author Correction: A consensus-based transparency checklist.
An amendment to this paper has been published and can be accessed via a link at the top of the paper
Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression
Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease
Characteristics of 263K Scrapie Agent in Multiple Hamster Species
Characteristics correlated better with host factors than with agent strain
From the CMD of Omega Centauri and (super-)AGB stellar models to a Galactic plane passage gas purging chemical evolution scenario
[Abbreviated] We have investigated the color-magnitude diagram of Omega
Centauri and find that the blue main sequence (bMS) can be reproduced only by
models that have a of helium abundance in the range Y=0.35-).
Y~0.35 must also be assumed in order to counteract the effects of high CNO on
turnoff colors, and thereby to obtain a good fit to the relatively blue turnoff
of this stellar population. This suggest a short chemical evolution period of
time (<1Gyr) for Omega Cen. Our intermediate-mass (super-)AGB models are able
to reproduce the high helium abundances, along with [N/Fe]~2 and substantial O
depletions if uncertainties in the treatment of convection are fully taken into
account. These abundance features distinguish the bMS stars from the dominant
[Fe/H] population. The most massive super-AGB stellar models
(M_zams>=6.8M_sun, M_He,core>=1.245M_sun) predict too large N-enhancements,
which limits their role in contributing to the extreme populations. We show
quantitatively that highly He- and N-enriched AGB ejecta have particularly
efficient cooling properties. Based on these results and on the reconstruction
of the orbit of Omega Cen with respect to the Milky Way we propose the galactic
plane passage gas purging scenario for the chemical evolution of this cluster.
Our model addresses the formation and properties of the bMS population
(including their central location in the cluster). We follow our model
descriptively through four passage events, which could explain not only some
key properties of the bMS, but also of the MS-a/RGB-a and the s-enriched stars.Comment: Accepted for publication in ApJ. 10 figures, 5 tables, 21 page
Catching Element Formation In The Act
Gamma-ray astronomy explores the most energetic photons in nature to address
some of the most pressing puzzles in contemporary astrophysics. It encompasses
a wide range of objects and phenomena: stars, supernovae, novae, neutron stars,
stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays
and relativistic-particle acceleration, and the evolution of galaxies. MeV
gamma-rays provide a unique probe of nuclear processes in astronomy, directly
measuring radioactive decay, nuclear de-excitation, and positron annihilation.
The substantial information carried by gamma-ray photons allows us to see
deeper into these objects, the bulk of the power is often emitted at gamma-ray
energies, and radioactivity provides a natural physical clock that adds unique
information. New science will be driven by time-domain population studies at
gamma-ray energies. This science is enabled by next-generation gamma-ray
instruments with one to two orders of magnitude better sensitivity, larger sky
coverage, and faster cadence than all previous gamma-ray instruments. This
transformative capability permits: (a) the accurate identification of the
gamma-ray emitting objects and correlations with observations taken at other
wavelengths and with other messengers; (b) construction of new gamma-ray maps
of the Milky Way and other nearby galaxies where extended regions are
distinguished from point sources; and (c) considerable serendipitous science of
scarce events -- nearby neutron star mergers, for example. Advances in
technology push the performance of new gamma-ray instruments to address a wide
set of astrophysical questions.Comment: 14 pages including 3 figure
A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
Peer reviewedPublisher PD
A consensus-based transparency checklist
We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository
Recommended from our members
Catching Element Formation In The Act
Gamma-ray astronomy explores the most energetic photons in nature to address
some of the most pressing puzzles in contemporary astrophysics. It encompasses
a wide range of objects and phenomena: stars, supernovae, novae, neutron stars,
stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays
and relativistic-particle acceleration, and the evolution of galaxies. MeV
gamma-rays provide a unique probe of nuclear processes in astronomy, directly
measuring radioactive decay, nuclear de-excitation, and positron annihilation.
The substantial information carried by gamma-ray photons allows us to see
deeper into these objects, the bulk of the power is often emitted at gamma-ray
energies, and radioactivity provides a natural physical clock that adds unique
information. New science will be driven by time-domain population studies at
gamma-ray energies. This science is enabled by next-generation gamma-ray
instruments with one to two orders of magnitude better sensitivity, larger sky
coverage, and faster cadence than all previous gamma-ray instruments. This
transformative capability permits: (a) the accurate identification of the
gamma-ray emitting objects and correlations with observations taken at other
wavelengths and with other messengers; (b) construction of new gamma-ray maps
of the Milky Way and other nearby galaxies where extended regions are
distinguished from point sources; and (c) considerable serendipitous science of
scarce events -- nearby neutron star mergers, for example. Advances in
technology push the performance of new gamma-ray instruments to address a wide
set of astrophysical questions
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