University of Iceland

About: University of Iceland is a education organization based out in Reykjavik, Suðurnes, Iceland. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 5423 authors who have published 16199 publications receiving 694762 citations. The organization is also known as: Háskóli Íslands.

Computationally efficient flux variability analysis

Abstract: Background Flux variability analysis is often used to determine robustness of metabolic models in various simulation conditions. However, its use has been somehow limited by the long computation time compared to other constraint-based modeling methods.

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Abstract: Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Genome-wide meta-analysis identifies new susceptibility loci for migraine

Abstract: Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls We identified 12 loci associated with migraine susceptibility (P<5×10(-8)) Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21 Three of these loci were identified in disease subgroup analyses Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B

Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index

Abstract: The epigenome consists of non–sequence-based modifications, such as DNA methylation, that are heritable during cell division and that may affect normal phenotypes and predisposition to disease. Here, we have performed an unbiased genome-scale analysis of ~4 million CpG sites in 74 individuals with comprehensive array-based relative methylation (CHARM) analysis. We found 227 regions that showed extreme interindividual variability [variably methylated regions (VMRs)] across the genome, which are enriched for developmental genes based on Gene Ontology analysis. Furthermore, half of these VMRs were stable within individuals over an average of 11 years, and these VMRs defined a personalized epigenomic signature. Four of these VMRs showed covariation with body mass index consistently at two study visits and were located in or near genes previously implicated in regulating body weight or diabetes. This work suggests an epigenetic strategy for identifying patients at risk of common disease.

Constraints on Cosmic-ray Propagation Models from A Global Bayesian Analysis

Abstract: Research in many areas of modern physics such as, e.g., indirect searches for dark matter and particle acceleration in supernova remnant shocks rely heavily on studies of cosmic rays (CRs) and associated diffuse emissions (radio, microwave, X-rays, γ-rays). While very detailed numerical models of CR propagation exist, a quantitative statistical analysis of such models has been so far hampered by the large computational effort that those models require. Although statistical analyses have been carried out before using semi-analytical models (where the computation is much faster), the evaluation of the results obtained from such models is difficult, as they necessarily suffer from many simplifying assumptions. The main objective of this paper is to present a working method for a full Bayesian parameter estimation for a numerical CR propagation model. For this study, we use the GALPROP code, the most advanced of its kind, which uses astrophysical information, and nuclear and particle data as inputs to self-consistently predict CRs, γ-rays, synchrotron, and other observables. We demonstrate that a full Bayesian analysis is possible using nested sampling and Markov Chain Monte Carlo methods (implemented in the SuperBayeS code) despite the heavy computational demands of a numerical propagation code. The best-fit values of parameters found in this analysis are in agreement with previous, significantly simpler, studies also based on GALPROP.