Meta-analysis on the association between genetic polymorphisms and prepulse inhibition of the acoustic startle response

Federal Ministry of Education and Research; German Research Network on Schizophrenia; Wellcome Trust; University of Crete; Manasaki and Propontis Scholarship Foundation

Large-scale gene-centric analysis identifies novel variants for coronary Artery disease

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10−33; LPA:p<10−19; 1p13.3:p<10−17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10−7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes

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

Genetic algorithm-based spinning reserve dispatching in a competitive electricity market

Power systems rely greatly on ancillary services in maintaining operation security. As one of the most important ancillary services, spinning reserve must be provided effectively in the deregulated market environment. This paper focuses on the design of an integrated market for both electricity and spinning reserve service with particular emphasis on coordinated dispatch of bulk power and spinning reserve services. A new market dispatching mechanism has been developed to minimize the ISO's total payment while ensuring system security. Genetic algorithms are used in the finding of the global optimal solutions for this dispatching problem. Case studies and corresponding analyses haw been carried out to demonstrate and discuss the efficiency and usefulness of the proposed market

Persistent differences in asthma self-efficacy by race, ethnicity, and income in adults with asthma

OBJECTIVE: The objective of this population-based study was to determine if and to what extent there are differences in asthma self-efficacy by race/ethnicity and income, and whether health status, levels of acculturation, and health care factors may explain these differences. METHODS: We conducted a secondary data analysis of asthma self-efficacy using the 2009 and 2011-2012 California Health Interview Survey, in adults with asthma (n = 7874). In order to examine if and how the effect of race /ethnicity and income on asthma self-efficacy may have been altered by health status, acculturation, and health care factors, we used staged multivariable logistic regression models. We conducted mediation analyses to evaluate which of these factors might mediate disparities in self-efficacy by race/ethnicity and income. RESULTS: 69.8% of adults reported having high asthma self-efficacy. Latinos (OR 0.66; 95% CI 0.51–0.86), African-Americans (OR 0.50; 95% CI 0.29–0.83), American Indian/Alaskan Natives (OR 0.55; 95% CI 0.31–0.98), and Asian/Pacific Islanders (OR 0.34; 95% CI 0.23–0.52) were less likely to report high self-efficacy compared to Whites. Individuals with income below the federal poverty level (OR 0.56; 95% CI 0.40-0.78) were less likely to report high self-efficacy compared to higher income individuals. The relationship between income and self-efficacy was no longer significant after further adjustment for health care factors; however, the differences in race and ethnicity persisted. Receiving an asthma management plan mediated the relationship in certain subgroups. CONCLUSIONS: Addressing modifiable health care factors may play an important role in reducing disparities in asthma self-efficacy

From Noncoding Variant to Phenotype via SORT1 at the 1p13 Cholesterol Locus

Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes.Stem Cell and Regenerative Biolog