Embracing polygenicity: a review of methods and tools for psychiatric genetics research.

The availability of genome-wide genetic data on hundreds of thousands of people has led to an equally rapid growth in methodologies available to analyse these data. While the motivation for undertaking genome-wide association studies (GWAS) is identification of genetic markers associated with complex traits, once generated these data can be used for many other analyses. GWAS have demonstrated that complex traits exhibit a highly polygenic genetic architecture, often with shared genetic risk factors across traits. New methods to analyse data from GWAS are increasingly being used to address a diverse set of questions about the aetiology of complex traits and diseases, including psychiatric disorders. Here, we give an overview of some of these methods and present examples of how they have contributed to our understanding of psychiatric disorders. We consider: (i) estimation of the extent of genetic influence on traits, (ii) uncovering of shared genetic control between traits, (iii) predictions of genetic risk for individuals, (iv) uncovering of causal relationships between traits, (v) identifying causal single-nucleotide polymorphisms and genes or (vi) the detection of genetic heterogeneity. This classification helps organise the large number of recently developed methods, although some could be placed in more than one category. While some methods require GWAS data on individual people, others simply use GWAS summary statistics data, allowing novel well-powered analyses to be conducted at a low computational burden

Resolution Tests of CsI(Tl) Scintillators Read Out by Pin Diodes

This research was sponsored by the National Science Foundation Grant NSF PHY 87-1440

Electromotive forces and the Meissner effect puzzle

In a voltaic cell, positive (negative) ions flow from the low (high) potential electrode to the high (low) potential electrode, driven by an `electromotive force' which points in opposite direction and overcomes the electric force. Similarly in a superconductor charge flows in direction opposite to that dictated by the Faraday electric field as the magnetic field is expelled in the Meissner effect. The puzzle is the same in both cases: what drives electric charges against electromagnetic forces? I propose that the answer is also the same in both cases: kinetic energy lowering, or `quantum pressure'

Phase separating binary fluids under oscillatory shear

We apply lattice Boltzmann methods to study the segregation of binary fluid mixtures under oscillatory shear flow in two dimensions. The algorithm allows to simulate systems whose dynamics is described by the Navier-Stokes and the convection-diffusion equations. The interplay between several time scales produces a rich and complex phenomenology. We investigate the effects of different oscillation frequencies and viscosities on the morphology of the phase separating domains. We find that at high frequencies the evolution is almost isotropic with growth exponents 2/3 and 1/3 in the inertial (low viscosity) and diffusive (high viscosity) regimes, respectively. When the period of the applied shear flow becomes of the same order of the relaxation time $T_R$ of the shear velocity profile, anisotropic effects are clearly observable. In correspondence with non-linear patterns for the velocity profiles, we find configurations where lamellar order close to the walls coexists with isotropic domains in the middle of the system. For particular values of frequency and viscosity it can also happen that the convective effects induced by the oscillations cause an interruption or a slowing of the segregation process, as found in some experiments. Finally, at very low frequencies, the morphology of domains is characterized by lamellar order everywhere in the system resembling what happens in the case with steady shear.Comment: 1 table and 12 figures in .gif forma

Macroscopic limits and phase transition in a system of self-propelled particles

We investigate systems of self-propelled particles with alignment interaction. Compared to previous work, the force acting on the particles is not normalized and this modification gives rise to phase transitions from disordered states at low density to aligned states at high densities. This model is the space inhomogeneous extension of a previous work by Frouvelle and Liu in which the existence and stability of the equilibrium states were investigated. When the density is lower than a threshold value, the dynamics is described by a non-linear diffusion equation. By contrast, when the density is larger than this threshold value, the dynamics is described by a hydrodynamic model for self-alignment interactions previously derived in Degond and Motsch. However, the modified normalization of the force gives rise to different convection speeds and the resulting model may lose its hyperbolicity in some regions of the state space

Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo

Major depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information Network initiative of the US Foundation for the National Institutes of Health, we conducted a genome-wide association study of 435 291 single nucleotide polymorphisms (SNPs) genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for MDD. Of the top 200, 11 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain) with P-values of 7.7 × 1

Zn-Neighbor Cu NQR in Zn-Substituted YBa2Cu3O7-d and YBa2Cu4O8

We studied local electronic states near Zn in optimally doped YBa$_2$(Cu$_{1-x}$Zn_x)$_3$O$_{7-\delta}$ and underdoped YBa$_2$(Cu$_{1-x}$Zn_x)$_4$O$_8$ via satellite signals of plane-site Cu(2) nuclear quadrupole resonance (NQR) spectra. From the relative intensity of Cu NQR spectra, the satellite signals are assigned to Zn-neighbor Cu NQR lines. The Cu nuclear spin-lattice relaxation time of the satellite signal is shorter than that of the main signal, which indicates that the magnetic correlation is locally enhanced near Zn both for the underdoped and the optimally doped systems. The pure YBa$_2$Cu$_4$O$_8$ is a stoichiometric, homogenous, underdoped electronic system; nevertheless, the Zn-induced inhomogeneous magnetic response in the CuO$_2$ plane is more marked than that of the optimally doped YBa$_2$Cu$_3$O$_{7-\delta}$.Comment: 9 pages including 8 figures, to be published in Phys. Rev.