A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings

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

Conservative Translations

In this paper we introduce the concept of conservative translation between logics. We present some necessary and sufficient conditions for a translation to be conservative and study some general properties of logical systems, these properties being characterized by the existence of conservative translations between the systems. We prove that the class constituted by logics and conservative translations between them determines a co-complete subcategory of the bi-complete category constituted by logics and translations. © 2001 Elsevier Science B.V.1081-3205227Carnielli, W.A., D'Ottaviano, I.M.L., Translations between logical systems: A manifesto (1997) Logique Anal., 40 (157), pp. 67-81D'Ottaviano, I.M.L., On the development of paraconsistent logic and da Costa's work (1990) J. Non-Classical Logic, 7 (1-2), pp. 9-72D'Ottaviano, I.M.L., Feitosa, H.A., Many-valued logics and translations (1999) J. Appl. Non-Classical Logics, 9 (1), pp. 121-140D'Ottaviano, I.M.L., Feitosa, H.A., (2000) Paraconsistent Logics and Translations, , Festschrift in honour of N.C.A. da Costa, to appearEpstein, R.L., (1990) The Semantic Foundations of Logic, Propositional Logics, 1. , Dordrecht: Kluwer Academic PublishersFeitosa, H.A., (1997) Traduções Conservativas, , (Conservative translations), Doctoral Thesis, Universidade Estadual de Campinas, CampinasGentzen, G., On the relation between intuitionistic and classical arithmetic (1969) The Collected Papers of Gerhard Gentzen, pp. 53-67. , M.E. Szabo. Amsterdam: North-HollandGlivenko, V., Sur quelques points de la logique de M. Brouwer (1929) Acad. Roy. Belgique, Bull. Classe Sci. Sér. 5, 15, pp. 183-188Gödel, K., On intuitionistic arithmetic and number theory (1933a) (1986) Collected Works, pp. 287-295. , S. et al. Feferman. Oxford: Oxford University PressGödel, K., An interpretation of the intuitionistic propositional calculus (1933b) (1986) Collected Works, pp. 301-303. , S. et al. Feferman. Oxford: Oxford University PressHeyting, A., Die formalen Regeln der intuitionistischen Logik, Sitzungsberichte der Preussischen (Berlin) Akademie der Wissenschaften (1930) Phys. Math., 1, pp. 42-56Hilbert, D., Die logischen grundlagen der mathematik (1923) Math. Ann., 88, pp. 151-165Johansson, I., Der Minimalkalkül, ein reduzierter intuitionistischer Formalismus (1936) Compositio Math., 4, pp. 119-136Kolmogoroff, A.N., On the principle of excluded middle (1925) (1977) From Frege to Gödel: A Source Book in Mathematical Logic, 1879-1931, pp. 414-437. , Heijenoort J. Cambridge: Harvard University PressMalinowski, G., (1993) Many-Valued Logics, , Oxford: Clarendon PressMcKinsey, J.C.C., Tarski, A., Some theorems about the sentential calculi of Lewis and Heyting (1948) J. Symbolic Logic, 13 (1), pp. 1-15Prawitz, D., Malmnäs, P.E., A survey of some connections between classical, intuitionistic and minimal logic (1968) Contributions to Mathematical Logic, pp. 215-229. , H. et al. Schmidt. Amsterdam: North-HollandRasiowa, H., Sikorski, R., (1953) The Mathematics of Metamathematics, , Waszawa: PWN - Polish Scientific PublishersSette, A.M., Carnielli, W.A., Maximal weakly-intuitionistic logic (1995) Stud. Logica, 55, pp. 181-203Da Silva, J.J., D'Ottaviano, I.M.L., Sette, A.M., Translations between logics (1999) Models, Algebras and Proofs, Lecture Notes in Pure and Applied Mathematics, 203, pp. 435-448. , X. Caicedo, Montenegro C.H. New York: Marcel DekkerSzabo, M.E., (1969) The Collected Papers of Gerhard Gentzen, Studies in Logic and the Foundations of Mathematics, , Amsterdam: North-HollandWójcicki, R., (1988) Theory of Logical Calculi: Basic Theory of Consequence Operations, Synthese Library, Vol. 199, , Dordrecht: Kluwer Academic Publisher

Three-valued logics in modal logic

<p>Every truth-functional three-valued propositional logic can be conservatively translated into the modal logic S5. We prove this claim constructively in two steps. First, we define a Translation Manual that converts any propositional formula of any three-valued logic into a modal formula. Second, we show that for every S5-model there is an equivalent three-valued valuation and vice versa. In general, our Translation Manual gives rise to translations that are exponentially longer than their originals. This fact raises the question whether there are three-valued logics for which there is a shorter translation into S5. The answer is affirmative: we present an elegant linear translation of the Logic of Paradox and of Strong Three-valued Logic into S5.</p>