Automated parameters for troubled-cell indicators using outlier detection

In Vuik and Ryan (2014) we studied the use of troubled-cell indicators for discontinuity detection in nonlinear hyperbolic partial differential equations and introduced a new multiwavelet technique to detect troubled cells. We found that these methods perform well as long as a suitable, problem-dependent parameter is chosen. This parameter is used in a threshold which decides whether or not to detect an element as a troubled cell. Until now, these parameters could not be chosen automatically. The choice of the parameter has impact on the approximation: it determines the strictness of the troubled-cell indicator. An inappropriate choice of the parameter will result in detection (and limiting) of too few or too many elements. The optimal parameter is chosen such that the minimal number of troubled cells is detected and the resulting approximation is free of spurious oscillations. In this paper we will see that for each troubled-cell indicator the sudden increase or decrease of the indicator value with respect to the neighboring values is important for detection. Indication basically reduces to detecting the outliers of a vector (one dimension) or matrix (two dimensions). This is done using Tukey's boxplot approach to detect which coefficients in a vector are straying far beyond others (Tukey, 1977). We provide an algorithm that can be applied to various troubled-cell indication variables. Using this technique the problem-dependent parameter that the original indicator requires is no longer necessary as the parameter will be chosen automatically

Selection against variants in the genome associated with educational attainment

Epidemiological and genetic association studies show that genetics play an important role in the attainment of education. Here, we investigate the effect of this genetic component on the reproductive history of 109,120 Icelanders and the consequent impact on the gene pool over time. We show that an educational attainment polygenic score, POLYEDU, constructed from results of a recent study is associated with delayed reproduction (P < 10-100) and fewer children overall. The effect is stronger for women and remains highly significant after adjusting for educational attainment. Based on 129,808 Icelanders born between 1910 and 1990, we find that the average POLYEDU has been declining at a rate of ∼0.010 standard units per decade, which is substantial on an evolutionary timescale. Most importantly, because POLYEDU only captures a fraction of the overall underlying genetic component the latter could be declining at a rate that is two to three times faster

Exploring predictive performance: A reanalysis of the geospace model transition challenge

The Pulkkinen et al. (2013) study evaluated the ability of five different geospace models to predict surface dB/dt as a function of upstream solar drivers. This was an important step in the assessment of research models for predicting and ultimately preventing the damaging effects of geomagnetically induced currents. Many questions remain concerning the capabilities of these models. This study presents a reanalysis of the Pulkkinen et al. (2013) results in an attempt to better understand the models’ performance. The range of validity of the models is determined by examining the conditions corresponding to the empirical input data. It is found that the empirical conductance models on which global magnetohydrodynamic models rely are frequently used outside the limits of their input data. The prediction error for the models is sorted as a function of solar driving and geomagnetic activity. It is found that all models show a bias toward underprediction, especially during active times. These results have implications for future research aimed at improving operational forecast models.Key PointsGeospace models of dB/dt frequently underpredict dB/dtOf five models tested, the SWMF is least likely to underpredict dB/dtEmpirical conductance models used by global MHD are frequently used outside their range of validityPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136305/1/swe20406.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136305/2/swe20406_am.pd

Genetic insight into sick sinus syndrome

Aims. The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Methods and results. We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10⁻²⁰), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05). Conclusion. We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS

A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

Bell et al. report 46 new loci associated with biomarkers of iron homeostasis, including ferritin levels, iron binding capacity, and iron saturation, in the Icelandic, Danish and UK populations. The associated loci point to new iron-regulating proteins and important genetic differences between men and women

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits

Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth