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      Hostility in adolescents and adults: a genome-wide association study of the Young Finns

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          Abstract

          Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15–30 years at phase 1 and 30–45 years at phase 4) in 982–1780 participants depending on the hostility measure. Few promising areas from chromosome 14 at 99 cM (top SNPs rs3783337, rs7158754, rs3783332, rs2181102, rs7159195, rs11160570, rs941898, P values <3.9 × 10 −8 with nearest gene Enah/Vasp-like ( EVL)) were found suggestively to be related to paranoia and from chromosome 7 at 86 cM (top SNPs rs802047, rs802028, rs802030, rs802026, rs802036, rs802025, rs802024, rs802032, rs802049, rs802051, P values <6.9 × 10 −7 with nearest gene CROT (carnitine O-octanoyltransferase)) to cynicism, respectively. Some shared suggestive genetic influence for both paranoia and cynicism was also found from chromosome 17 at 2.8 cM (SNPs rs12936442, rs894664, rs6502671, rs7216028) and chromosome 22 at 43 cM (SNPs rs7510759, rs7510924, rs7290560), with nearest genes RAP1 GTPase activating protein 2 ( RAP1GAP2) and KIAA1644, respectively. These suggestive associations did not replicate across all measurement times, which warrants further study on these SNPs in other populations.

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          Impact of Psychological Factors on the Pathogenesis of Cardiovascular Disease and Implications for Therapy

          Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.
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            The association of anger and hostility with future coronary heart disease: a meta-analytic review of prospective evidence.

            This review aimed to evaluate the association between anger and hostility and coronary heart disease (CHD) in prospective cohort studies using quantitative methods. The harmful effect of anger and hostility on CHD has been widely asserted, but previous reviews have been inconclusive. We searched general bibliographic databases: MEDLINE, PsycINFO, Web of Science, and PubMed up to November 2008. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. There were 25 studies (21 articles) investigating CHD outcomes in initially healthy populations and 19 studies (18 articles) of samples with existing CHD. Anger and hostility were associated with increased CHD events in the healthy population studies (combined hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.05 to 1.35, p = 0.008) and with poor prognosis in the CHD population studies (HR: 1.24; 95% CI: 1.08 to 1.42, p = 0.002). There were indications of publication bias in these reports, although the fail-safe numbers were 2,020 and 750 for healthy and disease population studies, respectively. Intriguingly, the harmful effect of anger and hostility on CHD events in the healthy populations was greater in men than women. In studies of participants with CHD at baseline that controlled fully for basal disease status and treatment, the association of anger and hostility with poor prognosis persisted. The current review suggests that anger and hostility are associated with CHD outcomes both in healthy and CHD populations. Besides conventional physical and pharmacological interventions, this supports the use of psychological management focusing on anger and hostility in the prevention and treatment of CHD.
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              A genotype calling algorithm for the Illumina BeadArray platform.

              Large-scale genotyping relies on the use of unsupervised automated calling algorithms to assign genotypes to hybridization data. A number of such calling algorithms have been recently established for the Affymetrix GeneChip genotyping technology. Here, we present a fast and accurate genotype calling algorithm for the Illumina BeadArray genotyping platforms. As the technology moves towards assaying millions of genetic polymorphisms simultaneously, there is a need for an integrated and easy-to-use software for calling genotypes. We have introduced a model-based genotype calling algorithm which does not rely on having prior training data or require computationally intensive procedures. The algorithm can assign genotypes to hybridization data from thousands of individuals simultaneously and pools information across multiple individuals to improve the calling. The method can accommodate variations in hybridization intensities which result in dramatic shifts of the position of the genotype clouds by identifying the optimal coordinates to initialize the algorithm. By incorporating the process of perturbation analysis, we can obtain a quality metric measuring the stability of the assigned genotype calls. We show that this quality metric can be used to identify SNPs with low call rates and accuracy. The C++ executable for the algorithm described here is available by request from the authors.
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                Author and article information

                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group
                2158-3188
                June 2011
                21 June 2011
                1 June 2011
                : 1
                : 6
                : e11
                Affiliations
                [1 ]simpleIBS, Unit of Personality, Work and Health Psychology, University of Helsinki , Helsinki, Finland
                [2 ]simpleDepartment of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital , Tampere, Finland
                [3 ]simpleMedical School, University of Tampere , Tampere, Finland
                [4 ]simpleFinnish Institute of Occupational Health , Helsinki, Finland
                [5 ]simpleTHL , Helsinki, Finland
                [6 ]simpleWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton , Cambridge, UK
                [7 ]simpleFIMM, Institute for Molecular Medicine Finland, University of Helsinki , Helsinki, Finland
                [8 ]simpleDepartment of Clinical Physiology, Tampere University Hospital , Tampere, Finland
                [9 ]simpleDepartment of Medicine, University of Turku and Turku University Hospital , Turku, Finland
                [10 ]simpleDepartment of Clinical Physiology, Turku University Hospital and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku , Turku, Finland
                Author notes
                [* ]simpleIBS, Unit of Personality, Work and Health Psychology, University of Helsinki, P.O. Box 9, FIN-00014 University of Helsinki , Helsinki, Finland. E-mail: liisa.keltikangas-jarvinen@ 123456helsinki.fi
                [✠]

                Deceased.

                Article
                tp201113
                10.1038/tp.2011.13
                3309462
                22832427
                1d753197-5b45-47aa-aa02-a46042c685b6
                Copyright © 2011 Macmillan Publishers Limited

                This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 06 May 2011
                : 10 May 2011
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                gene,gwas,personality,hostility,development
                Clinical Psychology & Psychiatry
                gene, gwas, personality, hostility, development

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