Risk factors for primary congenital glaucoma in the National Birth Defects Prevention Study

Primary congenital glaucoma (PCG) is a rare but serious birth defect. Genetic mutations have been implicated in the development of PCG, but little is known about nongenetic risk factors. This study investigates potential risk factors for PCG in the National Birth Defects Prevention Study (NBDPS), a large population-based case–control study of major birth defects in the United States. The analysis includes case infants with PCG (N = 107) and control infants without birth defects (N = 10,084) enrolled in NBDPS from birth years 2000–2011. Pregnancy/infant clinical characteristics, demographics, and parental health history were collected through maternal interview. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to examine associations with all PCG cases and isolated PCG cases without other major malformations. Associations with all the cases included term low birth weight (<2,500 g; aOR = 2.80, CI 1.59–4.94), non-Hispanic black maternal race/ethnicity (aOR = 2.42, CI 1.42–4.13), maternal history of seizure (aOR = 2.73, CI 1.25–5.97), maternal antihypertensive use (aOR = 3.60, CI 1.52–8.53), and maternal sexually transmitted infection (aOR = 2.75, CI 1.17–6.44). These factors were also associated with isolated PCG, as was maternal use of nonsteroidal anti-inflammatory drugs (aOR = 2.70, CI 1.15–6.34). This study is among the first to examine a wide array of potential risk factors for PCG in a population-based sample

Phantom Divide Crossing with General Non-minimal Kinetic Coupling

We propose a model of dark energy consists of a single scalar field with a general non-minimal kinetic couplings to itself and to the curvature. We study the cosmological dynamics of the equation of state in this setup. The coupling terms have the form $\xi_{1} R f(\phi)\partial_{\mu}\phi\partial^{\mu}\phi$ and $\xi_{2} R_{\mu\nu}f(\phi)\partial^{\mu}\phi\partial^{\nu}\phi$ where $\xi_{1}$ and $\xi_{2}$ are coupling parameters and their dimensions depend on the type of function $f(\phi)$. We obtain the conditions required for phantom divide crossing and show numerically that a cosmological model with general non-minimal derivative coupling to the scalar and Ricci curvatures can realize such a crossing.Comment: 12 pages, 4 figures. Accepted for publication in Gen. Rel. Grav. arXiv admin note: substantial text overlap with arXiv:1105.4967, arXiv:1201.1627, and with arXiv:astro-ph/0610092 by other author

Particle Physics Approach to Dark Matter

We review the main proposals of particle physics for the composition of the cold dark matter in the universe. Strong axion contribution to cold dark matter is not favored if the Peccei-Quinn field emerges with non-zero value at the end of inflation and the inflationary scale is superheavy since, under these circumstances, it leads to unacceptably large isocurvature perturbations. The lightest neutralino is the most popular candidate constituent of cold dark matter. Its relic abundance in the constrained minimal supersymmetric standard model can be reduced to acceptable values by pole annihilation of neutralinos or neutralino-stau coannihilation. Axinos can also contribute to cold dark matter provided that the reheat temperature is adequately low. Gravitinos can constitute the cold dark matter only in limited regions of the parameter space. We present a supersymmetric grand unified model leading to violation of Yukawa unification and, thus, allowing an acceptable b-quark mass within the constrained minimal supersymmetric standard model with mu>0. The model possesses a wide range of parameters consistent with the data on the cold dark matter abundance as well as other phenomenological constraints. Also, it leads to a new version of shifted hybrid inflation.Comment: 32 pages including 6 figures, uses svmult.cls, some clarifications added, lectures given at the Third Aegean Summer School "The Invisible Universe: Dark Matter and Dark Energy", 26 September-1 October 2005, Karfas, Island of Chios, Greece (to appear in the proceedings

Cluster Expansion Approach to the Effective Potential in Φ2+14\Phi^4_{2+1}-Theory

We apply a truncated set of dynamical equations of motion for connected equal-time Green functions up to the 4-point level to the investigation of spontaneous ground state symmetry breaking in $\Phi^4_{2+1}$ quantum field theory. Within our momentum space discretization we obtain a second order phase transition as soon as the connected 3-point function is included. However, an additional inclusion of the connected 4-point function still shows a significant influence on the shape of the effective potential and the critical coupling.Comment: 1 compressed uuencoded postscript file with 5 figures included, 21 page

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe