6,397 research outputs found
Estimating Effects and Making Predictions from Genome-Wide Marker Data
In genome-wide association studies (GWAS), hundreds of thousands of genetic
markers (SNPs) are tested for association with a trait or phenotype. Reported
effects tend to be larger in magnitude than the true effects of these markers,
the so-called ``winner's curse.'' We argue that the classical definition of
unbiasedness is not useful in this context and propose to use a different
definition of unbiasedness that is a property of the estimator we advocate. We
suggest an integrated approach to the estimation of the SNP effects and to the
prediction of trait values, treating SNP effects as random instead of fixed
effects. Statistical methods traditionally used in the prediction of trait
values in the genetics of livestock, which predates the availability of SNP
data, can be applied to analysis of GWAS, giving better estimates of the SNP
effects and predictions of phenotypic and genetic values in individuals.Comment: Published in at http://dx.doi.org/10.1214/09-STS306 the Statistical
Science (http://www.imstat.org/sts/) by the Institute of Mathematical
Statistics (http://www.imstat.org
Genetic architecture of body size in mammals
Much of the heritability for human stature is caused by mutations of small-to-medium effect. This is because detrimental pleiotropy restricts large-effect mutations to very low frequencies
Prediction of individual genetic risk to disease from genome-wide association studies
Empirical studies suggest that the effect sizes of individual causal risk alleles underlying complex genetic diseases are small, with most genotype relative risks in the range of 1.1-2.0. Although the increased risk of disease for a carrier is small for any single locus, knowledge of multiple-risk alleles throughout the genome could allow the identification of individuals that are at high risk. In this study, we investigate the number and effect size of risk loci that underlie complex disease constrained by the disease parameters of prevalence and heritability. Then we quantify the value of prediction of genetic risk to disease using a range of realistic combinations of the number, size, and distribution of risk effects that underlie complex diseases. We propose an approach to assess the genetic risk of a disease in healthy individuals, based on dense genome-wide SNP panels. We test this approach using simulation. When the number of loci contributing to the disease is >50, a large case-control study is needed to identify a set of risk loci for use in predicting the disease risk of healthy people not included in the case-control study. For diseases controlled by 1000 loci of mean relative risk of only 1.04, a case-control study with 10,000 cases and controls can lead to selection of ∼75 loci that explain >50% of the genetic variance. The 5% of people with the highest predicted risk are three to seven times more likely to suffer the disease than the population average, depending on heritability and disease prevalence. Whether an individual with known genetic risk develops the disease depends on known and unknown environmental factors
First normal stress difference and crystallization in a dense sheared granular fluid
The first normal stress difference () and the microstructure
in a dense sheared granular fluid of smooth inelastic hard-disks are probed
using event-driven simulations. While the anisotropy in the second moment of
fluctuation velocity, which is a Burnett-order effect, is known to be the
progenitor of normal stress differences in {\it dilute} granular fluids, we
show here that the collisional anisotropies are responsible for the normal
stress behaviour in the {\it dense} limit. As in the elastic hard-sphere
fluids, remains {\it positive} (if the stress is defined in
the {\it compressive} sense) for dilute and moderately dense flows, but becomes
{\it negative} above a critical density, depending on the restitution
coefficient. This sign-reversal of occurs due to the {\it
microstructural} reorganization of the particles, which can be correlated with
a preferred value of the {\it average} collision angle in the direction opposing the shear. We also report on the shear-induced
{\it crystal}-formation, signalling the onset of fluid-solid coexistence in
dense granular fluids. Different approaches to take into account the normal
stress differences are discussed in the framework of the relaxation-type
rheological models.Comment: 21 pages, 13 figure
EXTENDED SUPERCONFORMAL SYMMETRY, FREUDENTHAL TRIPLE SYSTEMS AND GAUGED WZW MODELS
We review the construction of extended ( N=2 and N=4 ) superconformal
algebras over triple systems and the gauged WZW models invariant under them.
The N=2 superconformal algebras (SCA) realized over Freudenthal triple systems
(FTS) admit extension to ``maximal'' N=4 SCA's with SU(2)XSU(2)XU(1) symmetry.
A detailed study of the construction and classification of N=2 and N=4 SCA's
over Freudenthal triple systems is given. We conclude with a study and
classification of gauged WZW models with N=4 superconformal symmetry.Comment: Invited talk presented at the Gursey Memorial Conference I in
Istanbul, Turkiye (June 6-10, 1994). To appear in the proceedings of the
conference. (21 pages. Latex document.
Scalar and tensorial topological matter coupled to (2+1)-dimensional gravity:A.Classical theory and global charges
We consider the coupling of scalar topological matter to (2+1)-dimensional
gravity. The matter fields consist of a 0-form scalar field and a 2-form tensor
field. We carry out a canonical analysis of the classical theory, investigating
its sectors and solutions. We show that the model admits both BTZ-like
black-hole solutions and homogeneous/inhomogeneous FRW cosmological
solutions.We also investigate the global charges associated with the model and
show that the algebra of charges is the extension of the Kac-Moody algebra for
the field-rigid gauge charges, and the Virasoro algebrafor the diffeomorphism
charges. Finally, we show that the model can be written as a generalized
Chern-Simons theory, opening the perspective for its formulation as a
generalized higher gauge theory.Comment: 40 page
Charges, Monopoles and Duality Relations
A charge-monopole theory is derived from simple and self-evident postulates.
Charges and monopoles take an analogous theoretical structure. It is proved
that charges interact with free waves emitted from monopoles but not with the
corresponding velocity fields. Analogous relations hold for monopole equations
of motion. The system's equations of motion can be derived from a regular
Lagrangian function.Comment: 17 pages + 3 figures
Reducing - duality to - duality
The infrared limit of Yang-Mills theory with compact gauge group
compactified on a two-torus is governed by an effective superconformal
field theory. We conjecture that this is a certain orbifold involving the
maximal torus of . Yang-Mills -duality makes predictions for all
correlators of this effective conformal field theory. These predictions are
shown to be implied by the standard -duality of the conformal field theory.
Consequently, Montonen-Olive duality between electric and magnetic states
reduces to the standard two-dimensional duality between momentum and winding
states.Comment: 13 pages, harvmac, no figures. (Some Comments added. Some references
added.
The target space geometry of N=(2,1) string theory
We describe the constraints on the target space
geometry of the heterotic superstring due to the left-moving
supersymmetry and currents. In the fermionic description of the internal
sector supersymmetry is realized quantum mechanically, so that both tree-level
and one-loop effects contribute to the order
constraints. We also discuss the physical interpretation of the resulting
target space geometry in terms of configurations of a -dimensional object
propagating in a -dimensional spacetime with a null isometry, which has
recently been suggested as a unified description of string and M theory.Comment: 41 pages, 5 figures, standard LaTeX, uses epsf.tex. Some typos
corrected, discussion in footnote 1 correcte
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