Institution
Icahn School of Medicine at Mount Sinai
Education•New York, New York, United States•
About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.
Topics: Population, Medicine, Cancer, Health care, Transplantation
Papers published on a yearly basis
Papers
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TL;DR: In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs, suggesting that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer.
Abstract: Background Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases. Purpose This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women. Methods We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer. Results Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE. Conclusion In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs. Implications These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far-reaching for public health intervention worldwide.
803 citations
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TL;DR: The novel coronavirus disease-2019 (COVID-19) has affected nearly every country worldwide and there are anecdotal observations of improved outcomes with systemic anticoagulation (AC), however, the specific outcomes are still unclear.
802 citations
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TL;DR: PRSice-2 is introduced, an efficient and scalable software program for automating and simplifying PRS analyses on large-scale data, and its combination of efficiency and power will be increasingly important as data sizes grow and as the applications of PRS become more sophisticated, e.g., when incorporated into high-dimensional or gene set–based analyses.
Abstract: BACKGROUND Polygenic risk score (PRS) analyses have become an integral part of biomedical research, exploited to gain insights into shared aetiology among traits, to control for genomic profile in experimental studies, and to strengthen causal inference, among a range of applications. Substantial efforts are now devoted to biobank projects to collect large genetic and phenotypic data, providing unprecedented opportunity for genetic discovery and applications. To process the large-scale data provided by such biobank resources, highly efficient and scalable methods and software are required. RESULTS Here we introduce PRSice-2, an efficient and scalable software program for automating and simplifying PRS analyses on large-scale data. PRSice-2 handles both genotyped and imputed data, provides empirical association P-values free from inflation due to overfitting, supports different inheritance models, and can evaluate multiple continuous and binary target traits simultaneously. We demonstrate that PRSice-2 is dramatically faster and more memory-efficient than PRSice-1 and alternative PRS software, LDpred and lassosum, while having comparable predictive power. CONCLUSION PRSice-2's combination of efficiency and power will be increasingly important as data sizes grow and as the applications of PRS become more sophisticated, e.g., when incorporated into high-dimensional or gene set-based analyses. PRSice-2 is written in C++, with an R script for plotting, and is freely available for download from http://PRSice.info.
802 citations
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Daniel Taliun1, Daniel N. Harris2, Michael D. Kessler2, Jedidiah Carlson3 +202 more•Institutions (61)
TL;DR: The Trans-Omics for Precision Medicine (TOPMed) project as discussed by the authors aims to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases.
Abstract: The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1 In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals) These rare variants provide insights into mutational processes and recent human evolutionary history The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 001% The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history
801 citations
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VU University Amsterdam1, Erasmus University Rotterdam2, Karolinska Institutet3, Charité4, Virginia Commonwealth University5, South London and Maudsley NHS Foundation Trust6, QIMR Berghofer Medical Research Institute7, King's College London8, University of Southern Denmark9, University of California, Riverside10, University of Southern California11, University of Minnesota12, University of Queensland13, University College London14, Johns Hopkins University15, University of California, Los Angeles16, University of Crete17, Harvard University18, Veterans Health Administration19, Icahn School of Medicine at Mount Sinai20, Yale University21, Haukeland University Hospital22, Trinity College, Dublin23, University of Edinburgh24, Hofstra University25, North Shore-LIJ Health System26, National Institutes of Health27, University of Bergen28, Oslo University Hospital29, National University of Ireland, Galway30, University of Helsinki31, University of Oslo32, Martin Luther University of Halle-Wittenberg33, Duke University34, National and Kapodistrian University of Athens35, Mental Health Research Institute36, University of Colorado Boulder37, Imperial College London38, University of Manchester39, Wellcome Trust40, Manchester Academic Health Science Centre41, Stanford University42, University of Oregon43, University of Toronto44, University of Michigan45, Erasmus University Medical Center46, Broad Institute47, University of North Carolina at Chapel Hill48
TL;DR: A large-scale genetic association study of intelligence identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure, a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
800 citations
Authors
Showing all 37948 results
Name | H-index | Papers | Citations |
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Robert Langer | 281 | 2324 | 326306 |
Shizuo Akira | 261 | 1308 | 320561 |
Gordon H. Guyatt | 231 | 1620 | 228631 |
Eugene Braunwald | 230 | 1711 | 264576 |
Bruce S. McEwen | 215 | 1163 | 200638 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Peter Libby | 211 | 932 | 182724 |
Mark J. Daly | 204 | 763 | 304452 |
Stuart H. Orkin | 186 | 715 | 112182 |
Paul G. Richardson | 183 | 1533 | 155912 |
Alan C. Evans | 183 | 866 | 134642 |
John C. Morris | 183 | 1441 | 168413 |
Paul M. Thompson | 183 | 2271 | 146736 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Bruce M. Psaty | 181 | 1205 | 138244 |