Vanderbilt University

About: Vanderbilt University is a education organization based out in Nashville, Tennessee, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 45066 authors who have published 106528 publications receiving 5435039 citations. The organization is also known as: Vandy.

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Abstract: Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors.

Drug-induced prolongation of the QT interval.

Abstract: The single most common cause of the withdrawal or restriction of the use of marketed drugs has been QT-interval prolongation associated with polymorphic ventricular tachycardia, or torsade de pointes, a condition that can be fatal. This review summarizes the current knowledge about molecular and clinical predictors of drug-induced QT-interval prolongation and torsade de pointes and discusses how new molecular predictors of drug action might be incorporated into drug-development programs and clinical practice. A general approach to drugs suspected of causing this problem is presented.

New Constraints on ΩM, ΩΛ, and w from an Independent Set of 11 High-Redshift Supernovae Observed with the Hubble Space Telescope*

Abstract: We report measurements of $\Omega_M$, $\Omega_\Lambda$, and w from eleven supernovae at z=0.36-0.86 with high-quality lightcurves measured using WFPC-2 on the HST. This is an independent set of high-redshift supernovae that confirms previous supernova evidence for an accelerating Universe. Combined with earlier Supernova Cosmology Project data, the new supernovae yield a flat-universe measurement of the mass density $\Omega_M=0.25^{+0.07}_{-0.06}$ (statistical) $\pm0.04$ (identified systematics), or equivalently, a cosmological constant of $\Omega_\Lambda=0.75^{+0.06}_{-0.07}$ (statistical) $\pm0.04$ (identified systematics). When the supernova results are combined with independent flat-universe measurements of $\Omega_M$ from CMB and galaxy redshift distortion data, they provide a measurement of $w=-1.05^{+0.15}_{-0.20}$ (statistical) $\pm0.09$ (identified systematic), if w is assumed to be constant in time. The new data offer greatly improved color measurements of the high-redshift supernovae, and hence improved host-galaxy extinction estimates. These extinction measurements show no anomalous negative E(B-V) at high redshift. The precision of the measurements is such that it is possible to perform a host-galaxy extinction correction directly for individual supernovae without any assumptions or priors on the parent E(B-V) distribution. Our cosmological fits using full extinction corrections confirm that dark energy is required with $P(\Omega_\Lambda>0)>0.99$, a result consistent with previous and current supernova analyses which rely upon the identification of a low-extinction subset or prior assumptions concerning the intrinsic extinction distribution.