A common variant near TGFBR3 is associated with primary open angle glaucoma

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Non-abelian T-dualizing the resolved conifold with regular and fractional D3-branes

Abstract: In this paper we obtain new solutions of Type IIA and massive Type IIA supergravity. These solutions are the result of implementing a non-abelian T-duality along the internal SU(2) isometries of several D3-brane configurations on the resolved conifold, studied by Pando Zayas and Tseytlin. We first study the pure NS resolved conifold solution, then we add fluxes by placing a stack of D3-branes at the tip of the resolved conifold and finally we consider the system of regular and fractional D3-branes at the tip. We present the non-abelian T-duals associated with these backgrounds and study their geometries and fluxes. We briefly comment on some field theory features by studying couplings and the central charge of the dual field theory. We also analyze the supersymmetry of the dual solutions and show that for the system of only D3 branes the duality defines a map between backgrounds with SU(3) and orthogonal SU(2) structures. © 2015, The Author(s)

Compactifications of the Klebanov-Witten CFT and new AdS3 backgrounds

In this paper we find various new backgrounds in Type IIB, IIA and M-theory with an AdS3-factor. The solutions are smooth and preserve small amounts of SUSY. These new backgrounds are found by application of non-Abelian T-duality (sometimes combined with T-duality) on the supergravity solution dual to the Klebanov-Witten CFT compactified to two dimensions. The field theory aspects encoded by these backgrounds are studied. We give a detailed account of conserved charges, central charges, entanglement entropy and Wilson loops. Further, we present a possible field theory interpretation for our backgrounds. © 2015, The Author(s)

The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics research.

Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections. To facilitate exploratory genetics research, we have assembled a DNA resource from a large number of subjects participating in multiple studies throughout the world. This growing resource was initially genotyped with a commercially available genome-wide 500,000 single-nucleotide polymorphism panel. This project includes nearly 6,000 subjects of African-American, East Asian, South Asian, Mexican, and European origin. Seven informative axes of variation identified via principal-component analysis (PCA) of these data confirm the overall integrity of the data and highlight important features of the genetic structure of diverse populations. The potential value of such extensively genotyped collections is illustrated by selection of genetically matched population controls in a genome-wide analysis of abacavir-associated hypersensitivity reaction. We find that matching based on country of origin, identity-by-state distance, and multidimensional PCA do similarly well to control the type I error rate. The genotype and demographic data from this reference sample are freely available through the NCBI database of Genotypes and Phenotypes (dbGaP)

Qualidade de frutos de tomateiro fertirrigado com potássio em solo co berto com polietileno preto.

O objetivo deste estudo foi determinar os efeitos da fertirrigação potássica e da cobertura do solo com polietileno preto na composi ção e qualidade de frutos de tomate. O experimento foi realizado nos meses de setembro de 1995 a janeiro de 1996, compreendendo o final do período fiio e seco e o início do período quente e chuvoso, na Universidade Federal de Viçosa, em solo podzólico vermelho- amarelo câmbico. Os tratamentos, com cinco repetições, no delinea mento em blocos casualizados, foram: (A) aplicação manual de 40% da dose recomendada de K no sulco de transplante e 60% aplicados manualmente, em cobertura (testemunha); (B) aplicação manual de 40% da dose de K no sulco de transplante e 60% aplicados por fertirrigação; (C) aplicação manual de 40% da dose de K no sulco de transplante e 60% aplicados por fertirrigação, em solo coberto com polietileno preto; (D) aplicação de 100% da dose de K por fertirrigação e (E) aplicação de 100% da dose de K por fertirrigação, em solo coberto com polietileno preto. Cada unidade experimental foi constituída por 28 plantas no espaçamento 1,0 x 0,5 m, sendo a parcela útil formada pelas 10 plantas centrais. A percentagem de matéria seca e os teores de N-NH4+, N-N03_, N-total, P, K, S, Mg e relação K/Ca na matéria seca do fruto de tomate não foram influen ciados pela fertirrigação e pela cobertura do solo com polietileno. Com a aplicação total do K por fertirrigação, o teor de Ca no fruto foi maior com o uso da cobertura do solo com polietileno. Por outro lado, as relações K/Mg e K/(Ca+Mg) no fruto foram, em geral, me nores no tratamento com fertirrigação total e com polietileno. A per centagem de sólidos solúveis totais, a acidez total titulável, o "flavor", o pH e o teor de vitamina C no fruto de tomate não foram influenci ados pela fertirrigação e pela cobertura do solo com polietileno, en quanto os teores de licopeno e carotenóides totais, quando a fertirrigação potássica foi total, aumentaram com o uso da cobertura do solo