Gauging CSO groups in N=4 Supergravity

We investigate a class of CSO-gaugings of N=4 supergravity coupled to six vector multiplets. Using the CSO-gaugings we do not find a vacuum that is stable against all scalar perturbations at the point where the matter fields are turned off. However, at this point we do find a stable cosmological scaling solution.Comment: 21 page

Group Manifold Reduction of Dual N=1 d=10 Supergravity

We perform a group manifold reduction of the dual version of N=1 d=10 supergravity to four dimensions. The effects of the 3- and 4-form gauge fields in the resulting gauged N=4 d=4 supergravity are studied in particular. The example of the group manifold SU(2)xSU(2) is worked out in detail, and we compare for this case the four-dimensional scalar potential with gauged N=4 supergravity.Comment: 22 pages, revised section 3, typos corrected. Published versio

De Sitter solutions in N=4 matter coupled supergravity

We investigate the scalar potential of gauged N=4 supergravity with matter. The extremum in the SU(1,1)/U(1) scalars is obtained for an arbitrary number of matter multiplets. The constraints on the matter scalars are solved in terms of an explicit parametrisation of an SO(6,6+n) element. For the case of six matter multiplets we discuss both compact and noncompact gauge groups. In an example involving noncompact groups and four scalars we find a potential with an absolute minimum and a positive cosmological constant.Comment: 14 page

Potential and mass-matrix in gauged N=4 supergravity

We discuss the potential and mass-matrix of gauged N=4 matter coupled supergravity for the case of six matter multiplets, extending previous work by considering the dependence on all scalars. We consider all semi-simple gauge groups and analyse the potential and its first and second derivatives in the origin of the scalar manifold. Although we find in a number of cases an extremum with a positive cosmological constant, these are not stable under fluctuations of all scalar fields.Comment: 28 pages, LaTe

Dynamics of Generalized Assisted Inflation

We study the dynamics of multiple scalar fields and a barotropic fluid in an FLRW-universe. The scalar potential is a sum of exponentials. All critical points are constructed and these include scaling and de Sitter solutions. A stability analysis of the critical points is performed for generalized assisted inflation, which is an extension of assisted inflation where the fields mutually interact. Effects in generalized assisted inflation which differ from assisted inflation are emphasized. One such a difference is that an (inflationary) attractor can exist if some of the exponential terms in the potential are negative.Comment: 27 page

Scaling Cosmologies of N=8 Gauged Supergravity

We construct exact cosmological scaling solutions in N=8 gauged supergravity. We restrict to solutions for which the scalar fields trace out geodesic curves on the scalar manifold. Under these restrictions it is shown that the axionic scalars are necessarily constant. The potential is then a sum of exponentials and has a very specific form that allows for scaling solutions. The scaling solutions describe eternal accelerating and decelerating power-law universes, which are all unstable. An uplift of the solutions to 11-dimensional supergravity is carried out and the resulting timedependent geometries are discussed. In the discussion we briefly comment on the fact that N=2 gauged supergravity allows stable scaling solutions.Comment: 17 pages; referenced added, reportnr changed and some corrections in section

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (P = 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association