BOOST: A fast approach to detecting gene-gene interactions in genome-wide case-control studies

Gene-gene interactions have long been recognized to be fundamentally important to understand genetic causes of complex disease traits. At present, identifying gene-gene interactions from genome-wide case-control studies is computationally and methodologically challenging. In this paper, we introduce a simple but powerful method, named `BOolean Operation based Screening and Testing'(BOOST). To discover unknown gene-gene interactions that underlie complex diseases, BOOST allows examining all pairwise interactions in genome-wide case-control studies in a remarkably fast manner. We have carried out interaction analyses on seven data sets from the Wellcome Trust Case Control Consortium (WTCCC). Each analysis took less than 60 hours on a standard 3.0 GHz desktop with 4G memory running Windows XP system. The interaction patterns identified from the type 1 diabetes data set display significant difference from those identified from the rheumatoid arthritis data set, while both data sets share a very similar hit region in the WTCCC report. BOOST has also identified many undiscovered interactions between genes in the major histocompatibility complex (MHC) region in the type 1 diabetes data set. In the coming era of large-scale interaction mapping in genome-wide case-control studies, our method can serve as a computationally and statistically useful tool.Comment: Submitte

Melting of Flux Lines in an Alternating Parallel Current

We use a Langevin equation to examine the dynamics and fluctuations of a flux line (FL) in the presence of an {\it alternating longitudinal current} $J_{\parallel}(\omega)$. The magnus and dissipative forces are equated to those resulting from line tension, confinement in a harmonic cage by neighboring FLs, parallel current, and noise. The resulting mean-square FL fluctuations are calculated {\it exactly}, and a Lindemann criterion is then used to obtain a nonequilibrium `phase diagram' as a function of the magnitude and frequency of $J_{\parallel}(\omega)$. For zero frequency, the melting temperature of the mixed phase (a lattice, or the putative "Bose" or "Bragg Glass") vanishes at a limiting current. However, for any finite frequency, there is a non-zero melting temperature.Comment: 5 pages, 1 figur

A decade in review after Idiopathic Scoliosis was first called a complex trait-A tribute to the late Dr. Yves Cotrel for his support in studies of etiology of scoliosis

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development

A decade in review after Idiopathic Scoliosis was first called a complex trait-A tribute to the late Dr. Yves Cotrel for his support in studies of etiology of scoliosis

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development

XY models with disorder and symmetry-breaking fields in two dimensions

The combined effect of disorder and symmetry-breaking fields on the two-dimensional XY model is examined. The study includes disorder in the interaction among spins in the form of random phase shifts as well as disorder in the local orientation of the field. The phase diagrams are determined and the properties of the various phases and phase transitions are calculated. We use a renormalization group approach in the Coulomb gas representation of the model. Our results differ from those obtained for special cases in previous works. In particular, we find a changed topology of the phase diagram that is composed of phases with long-range order, quasi-long-range order, and short-range order. The discrepancies can be ascribed to a breakdown of the fugacity expansion in the Coulomb gas representation. Implications for physical systems such as planar Josephson junctions and the faceting of crystal surfaces are discussed.Comment: 17 pages Latex with 5 eps figures, change: acknowledgment extende

Dynamic renormalization group study of a generalized continuum model of crystalline surfaces

We apply the Nozieres-Gallet dynamic renormalization group (RG) scheme to a continuum equilibrium model of a d-dimensional surface relaxing by linear surface tension and linear surface diffusion, and which is subject to a lattice potential favoring discrete values of the height variable. The model thus interpolates between the overdamped sine-Gordon model and a related continuum model of crystalline tensionless surfaces. The RG flow predicts the existence of an equilibrium roughening transition only for d = 2 dimensional surfaces, between a flat low-temperature phase and a rough high-temperature phase in the Edwards-Wilkinson (EW) universality class. The surface is always in the flat phase for any other substrate dimensions d > 2. For any value of d, the linear surface diffusion mechanism is an irrelevant perturbation of the linear surface tension mechanism, but may induce long crossovers within which the scaling properties of the linear molecular-beam epitaxy equation are observed, thus increasing the value of the sine-Gordon roughening temperature. This phenomenon originates in the non-linear lattice potential, and is seen to occur even in the absence of a bare surface tension term. An important consequence of this is that a crystalline tensionless surface is asymptotically described at high temperatures by the EW universality class.Comment: 22 pages, 5 figures. Accepted for publication in Physical Review

Non-Hermitian Localization and Population Biology

The time evolution of spatial fluctuations in inhomogeneous d-dimensional biological systems is analyzed. A single species continuous growth model, in which the population disperses via diffusion and convection is considered. Time-independent environmental heterogeneities, such as a random distribution of nutrients or sunlight are modeled by quenched disorder in the growth rate. Linearization of this model of population dynamics shows that the fastest growing localized state dominates in a time proportional to a power of the logarithm of the system size. Using an analogy with a Schrodinger equation subject to a constant imaginary vector potential, we propose a delocalization transition for the steady state of the nonlinear problem at a critical convection threshold separating localized and extended states. In the limit of high convection velocity, the linearized growth problem in $d$ dimensions exhibits singular scaling behavior described by a (d-1)-dimensional generalization of the noisy Burgers' equation, with universal singularities in the density of states associated with disorder averaged eigenvalues near the band edge in the complex plane. The Burgers mapping leads to unusual transverse spreading of convecting delocalized populations.Comment: 22 pages, 11 figure

Anisotropic Scaling in Threshold Critical Dynamics of Driven Directed Lines

The dynamical critical behavior of a single directed line driven in a random medium near the depinning threshold is studied both analytically (by renormalization group) and numerically, in the context of a Flux Line in a Type-II superconductor with a bulk current $\vec J$. In the absence of transverse fluctuations, the system reduces to recently studied models of interface depinning. In most cases, the presence of transverse fluctuations are found not to influence the critical exponents that describe longitudinal correlations. For a manifold with $d=4-\epsilon$ internal dimensions, longitudinal fluctuations in an isotropic medium are described by a roughness exponent $\zeta_\parallel=\epsilon/3$ to all orders in $\epsilon$, and a dynamical exponent $z_\parallel=2-2\epsilon/9+O(\epsilon^2)$. Transverse fluctuations have a distinct and smaller roughness exponent $\zeta_\perp=\zeta_\parallel-d/2$ for an isotropic medium. Furthermore, their relaxation is much slower, characterized by a dynamical exponent $z_\perp=z_\parallel+1/\nu$, where $\nu=1/(2-\zeta_\parallel)$ is the correlation length exponent. The predicted exponents agree well with numerical results for a flux line in three dimensions. As in the case of interface depinning models, anisotropy leads to additional universality classes. A nonzero Hall angle, which has no analogue in the interface models, also affects the critical behavior.Comment: 26 pages, 8 Postscript figures packed together with RevTeX 3.0 manuscript using uufiles, uses multicol.sty and epsf.sty, e-mail [email protected] in case of problem

Bond and charge density waves in the isotropic interacting two-dimensional quarter-filled band and the insulating state proximate to organic superconductivity

We report two surprising results regarding the nature of the spatial broken symmetries in the two-dimensional (2D), quarter-filled band with strong electron-electron interactions. First, in direct contradiction to the predictions of one-electron theory, we find a coexisting ``bond-order and charge density wave'' (BCDW) insulating ground state in the 2D rectangular lattice for all anisotropies, including the isotropic limit. Second, we find that the BCDW further coexists with a spin-density wave (SDW) in the range of large anisotropy. Further, in contrast to the interacting half-filled band, in the interacting quarter-filled band there are two transitions: first, a similar singlet-to-AFM/SDW transition for large anisotropy and second, an AFM/SDW-to-singlet transition at smaller anisotropy. We discuss how these theoretical results apply to the insulating states that are proximate to the superconducting states of 2:1 cationic charge-transfer solids (CTS). An important consequence of this work is the suggestion that organic superconductivity is related to the proximate Coulomb-induced BCDW, with the SDW that coexists for large anisotropies being also a consequence of the BCDW, rather than the driver of superconductivity.Comment: 29 pages, 18 eps figures. Revised with new appendices; to appear in Phys. Rev. B 62, Nov 15, 200

Nature of the Low Field Transition in the Mixed State of High Temperature Superconductors

We have numerically studied the statics and dynamics of a model three-dimensional vortex lattice at low magnetic fields. For the statics we use a frustrated 3D XY model on a stacked triangular lattice. We model the dynamics as a coupled network of overdamped resistively-shunted Josephson junctions with Langevin noise. At low fields, there is a weakly first-order phase transition, at which the vortex lattice melts into a line liquid. Phase coherence parallel to the field persists until a sharp crossover, conceivably a phase transition, near $T_{\ell} > T_m$ which develops at the same temperature as an infinite vortex tangle. The calculated flux flow resistivity in various geometries near $T=T_{\ell}$ closely resembles experiment. The local density of field induced vortices increases sharply near $T_\ell$, corresponding to the experimentally observed magnetization jump. We discuss the nature of a possible transition or crossover at $T_\ell$(B) which is distinct from flux lattice melting.Comment: Updated references. 46 pages including low quality 25 eps figures. Contact [email protected] or visit http://www.physics.ohio-state.edu:80/~ryu/ for better figures and additional movie files from simulations. To be published in Physical Review B1 01Jun9