Familial aggregation and heritability of type 1 diabetes mellitus and coaggregation of chronic diseases in affected families

Purpose: To estimate the extent of familial aggregation of type 1 diabetes (T1D) and coaggregation of related chronic diseases and assess the relative contribution of environmental and genetic factors on the risks. Patients and methods: This population-based study used the Taiwan National Health Insurance database to reconstruct family structure and identify people with T1D and other chronic diseases between 1999 and 2015. Relative risks (RRs) for T1D and other chronic diseases and heritability of T1D were estimated. Heritability was estimated using the polygenic liability model. Results: Validation of family structure found the positive predictive value to be 98.7% for maternal links and 98.6% for paternal links. Having an affected twin, first-degree relative, or spouse was associated with an adjusted RR (95% CI) of 553.66 (427.59-716.89), 32.49 (28.66-36.84), and 2.17 (0.31-15.40) for T1D, respectively. Based on the polygenic liability model, heritability, shared and non-shared contributions to T1D, and variances were 66.50%, 10.86%, and 22.64%, respectively. A family history of T1D was associated with an RR (95% CI) of 1.51 (1.20-1.89) for rheumatoid arthritis, 1.66 (1.21-2.26) for Sjogren's syndrome, 1.48 (1.09-2.01) for systemic lupus erythematosus, 1.24 (1.14-1.35) for simple goiter, 1.16 (1.04-1.31) for non-toxic nodular goiter, 1.61 (1.49-1.74) for thyrotoxicosis, 1.78 (1.57-2.01) for acquired hypothyroidism, 1.66 (1.40-1.98) for thyroiditis, and 1.15 (0.97-1.37) for epilepsy. Conclusion: These data highlight the importance of the genetic contribution to T1D and confirm the coaggregation of autoimmune and metabolic diseases with T1D

A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: The Treat-OA consortium

To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genomewide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81×10-5). The C allele conferred a reduced risk of 33% to 41% using a case-control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory

The advent of the Auger Engineering Radio Array (AERA) necessitates the development of a powerful framework for the analysis of radio measurements of cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air shower radio emission in coincidence with the surface particle detectors and fluorescence telescopes of the Pierre Auger Observatory, the radio analysis functionality had to be incorporated in the existing hybrid analysis solutions for fluoresence and surface detector data. This goal has been achieved in a natural way by extending the existing Auger Offline software framework with radio functionality. In this article, we lay out the design, highlights and features of the radio extension implemented in the Auger Offline framework. Its functionality has achieved a high degree of sophistication and offers advanced features such as vectorial reconstruction of the electric field, advanced signal processing algorithms, a transparent and efficient handling of FFTs, a very detailed simulation of detector effects, and the read-in of multiple data formats including data from various radio simulation codes. The source code of this radio functionality can be made available to interested parties on request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to author list and references in v

Reducing scattered light in LIGO's third observing run

Published 14 December 2020Noise due to scattered light has been a frequent disturbance in the advanced LIGO gravitational wave detectors, hindering the detection of gravitational waves. The non stationary scatter noise caused by low frequency motion can be recognized as arches in the time-frequency plane of the gravitational wave channel. In this paper,we characterize the scattering noise for LIGOandVirgo’s third observing run O3 from April, 2019 to March, 2020. We find at least two different populations of scattering noise and we investigate the multiple origins of one of them as well as itsmitigation.We find that relativemotion between two specific surfaces is strongly correlated with the presence of scattered light and we implement a technique to reduce this motion.We also present an algorithm using a witness channel to identify the times this noise can be present in the detector.S. Soni ... D D Brown ... A A Ciobanu ... D J Ottaway ... P J Veitch ... et al. (The LIGO Scientific Collaboration

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs49654

Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK 1803

Regional climate and vegetation response to orbital forcing within the mid-Pliocene Warm Period: A study using HadCM3

Regional climate and environmental variability in response to orbital forcing during interglacial events within the mid-Piacenzian (Pliocene) Warm Period (mPWP; 3.264–3.025 Ma) has been rarely studied using climate and vegetation models. Here we use climate and vegetation model simulations to predict changes in regional vegetation patterns in response to orbital forcing for four different interglacial events within the mPWP (Marine Isotope Stages (MIS) G17, K1, KM3 and KM5c). The efficacy of model-predicted changes in regional vegetation is assessed by reference to selected high temporal resolution palaeobotanical studies that are theoretically capable of discerning vegetation patterns for the selected interglacial stages. Annual mean surface air temperatures for the studied interglacials are between 0.4 °C to 0.7 °C higher than a comparable Pliocene experiment using modern orbital parameters. Increased spring/summer and reduced autumn/winter insolation in the Northern Hemisphere during MIS G17, K1 and KM3 enhances seasonality in surface air temperature. The two most robust and notable regional responses to this in vegetation cover occur in North America and continental Eurasia, where forests are replaced by more open-types of vegetation (grasslands and shrubland). In these regions our model results appear to be inconsistent with local palaeobotanical data. The orbitally driven changes in seasonal temperature and precipitation lead to a ~ 30% annual reduction in available deep soil moisture (2.0 m from surface), a critical parameter for forest growth, and subsequent reduction in the geographical coverage of forest-type vegetation; a phenomenon not seen in comparable simulations of Pliocene climate and vegetation run with a modern orbital configuration. Our results demonstrate the importance of examining model performance under a range of realistic orbital forcing scenarios within any defined time interval (e.g. mPWP). Additional orbitally resolved records of regional vegetation are needed to further examine the validity of model-predicted regional climate and vegetation responses in greater detail