Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Galaxy bulges and their massive black holes: a review

With references to both key and oft-forgotten pioneering works, this article starts by presenting a review into how we came to believe in the existence of massive black holes at the centres of galaxies. It then presents the historical development of the near-linear (black hole)-(host spheroid) mass relation, before explaining why this has recently been dramatically revised. Past disagreement over the slope of the (black hole)-(velocity dispersion) relation is also explained, and the discovery of sub-structure within the (black hole)-(velocity dispersion) diagram is discussed. As the search for the fundamental connection between massive black holes and their host galaxies continues, the competing array of additional black hole mass scaling relations for samples of predominantly inactive galaxies are presented.Comment: Invited (15 Feb. 2014) review article (submitted 16 Nov. 2014). 590 references, 9 figures, 25 pages in emulateApJ format. To appear in "Galactic Bulges", E. Laurikainen, R.F. Peletier, and D.A. Gadotti (eds.), Springer Publishin

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults

Attention deficit hyperactivity disorder (ADHD) is accompanied by resting-state alterations, including abnormal activity, connectivity and asymmetry of the default-mode network (DMN). Concurrently, recent studies suggested a link between ADHD and the presence of polymorphisms within the gene BAIAP2 (i.e., brain-specific angiogenesis inhibitor 1-associated protein 2), known to be differentially expressed in brain hemispheres. The clinical and neuroimaging correlates of this polymorphism are still unknown. We investigated the association between BAIAP2 polymorphisms and DMN functional connectivity (FC) asymmetry as well as behavioral measures in ADHD adults. Resting-state fMRI was acquired from 30 ADHD and 15 healthy adults. For each subject, rs7210438 and rs8079626 within the gene BAIAP2 were genotyped. ADHD severity, impulsiveness and anger were assessed for the ADHD group. Using multivariate analysis of variance, we found that genetic features do have an impact on DMN FC asymmetry. In particular, polymorphism rs8079626 affects medial frontal gyrus and inferior parietal lobule connectivity asymmetry, lower for AA than AG/GG carriers. Further, when combining FC asymmetry and the presence of the rs8079626 variant, we successfully predicted increased externalization of anger in ADHD. In conclusion, a complex interplay between genetic vulnerability and inter-hemispherical DMN FC asymmetry plays a role in emotion regulation in adult ADHD

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Population structure and resistance to mefenoxam of Phytophthora capsici in New York State

In 2006, 2007, and 2008, we sampled 257 isolates of Phytophthora capsici from vegetables at 22 sites in four regions of New York, to determine variation in mefenoxam resistance and population genetic structure. Isolates were assayed for mefenoxam resistance and genotyped for mating type and five microsatellite loci. We found mefenoxam-resistant isolates at a high frequency in the Capital District and Long Island, but none were found in western New York or central New York. Both A1 and A2 mating types were found at 12 of the 22 sites, and we detected 126 distinct multilocus genotypes, only nine of which were found at more than one site. Significant differentiation (FST) was found in more than 98% of the pairwise comparisons between sites; approximately 24 and 16% of the variation in the population was attributed to differences among regions and sites, respectively. These results indicate that P. capsici in New York is highly diverse, but gene flow among regions and fields is restricted. Therefore, each field needs to be considered an independent population, and efforts to prevent movement of inoculum among fields need to be further emphasized to prevent the spread of this pathogen. © 2010 The American Phytopathological Society.Articl