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  1. AU="Joanne B. Cole"
  2. AU="Steiger Patrick"
  3. AU="Dashti, Kobra"
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  1. Article ; Online: Comprehensive genomic analysis of dietary habits in UK Biobank identifies hundreds of genetic associations

    Joanne B. Cole / Jose C. Florez / Joel N. Hirschhorn

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: The choice of food intake is at least partially influenced by genetics, even though the effect sizes appear rather modest. Here, Cole et al. perform GWAS for food intake (85 individual food items and 85 derived dietary patterns) and test potential causal ...

    Abstract The choice of food intake is at least partially influenced by genetics, even though the effect sizes appear rather modest. Here, Cole et al. perform GWAS for food intake (85 individual food items and 85 derived dietary patterns) and test potential causal relationships with cardiometabolic traits using Mendelian randomization.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Comprehensive genomic analysis of dietary habits in UK Biobank identifies hundreds of genetic associations

    Joanne B. Cole / Jose C. Florez / Joel N. Hirschhorn

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: The choice of food intake is at least partially influenced by genetics, even though the effect sizes appear rather modest. Here, Cole et al. perform GWAS for food intake (85 individual food items and 85 derived dietary patterns) and test potential causal ...

    Abstract The choice of food intake is at least partially influenced by genetics, even though the effect sizes appear rather modest. Here, Cole et al. perform GWAS for food intake (85 individual food items and 85 derived dietary patterns) and test potential causal relationships with cardiometabolic traits using Mendelian randomization.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Cardiometabolic risk factors for COVID-19 susceptibility and severity

    Aaron Leong / Joanne B Cole / Laura N Brenner / James B Meigs / Jose C Florez / Josep M Mercader

    PLoS Medicine, Vol 18, Iss 3, p e

    A Mendelian randomization analysis.

    2021  Volume 1003553

    Abstract: Background Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID- ... ...

    Abstract Background Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses. Methods and findings We selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10-8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank: odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10-5; UK Biobank: odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10-5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null. Conclusions In this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  4. Article ; Online: The impact of non-additive genetic associations on age-related complex diseases

    Marta Guindo-Martínez / Ramon Amela / Silvia Bonàs-Guarch / Montserrat Puiggròs / Cecilia Salvoro / Irene Miguel-Escalada / Caitlin E. Carey / Joanne B. Cole / Sina Rüeger / Elizabeth Atkinson / Aaron Leong / Friman Sanchez / Cristian Ramon-Cortes / Jorge Ejarque / Duncan S. Palmer / Mitja Kurki / FinnGen Consortium / Krishna Aragam / Jose C. Florez /
    Rosa M. Badia / Josep M. Mercader / David Torrents

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Most genome-wide association studies assume an additive model, exclude the X chromosome, and use one reference panel. Here, the authors implement a strategy including non-additive models and find that the number of loci for age-related traits increases ... ...

    Abstract Most genome-wide association studies assume an additive model, exclude the X chromosome, and use one reference panel. Here, the authors implement a strategy including non-additive models and find that the number of loci for age-related traits increases as compared to the additive model alone.
    Keywords Science ; Q
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes

    Miriam S Udler / Jaegil Kim / Marcin von Grotthuss / Sílvia Bonàs-Guarch / Joanne B Cole / Joshua Chiou / Christopher D. Anderson on behalf of METASTROKE and the ISGC / Michael Boehnke / Markku Laakso / Gil Atzmon / Benjamin Glaser / Josep M Mercader / Kyle Gaulton / Jason Flannick / Gad Getz / Jose C Florez

    PLoS Medicine, Vol 15, Iss 9, p e

    A soft clustering analysis.

    2018  Volume 1002654

    Abstract: Background Type 2 diabetes (T2D) is a heterogeneous disease for which (1) disease-causing pathways are incompletely understood and (2) subclassification may improve patient management. Unlike other biomarkers, germline genetic markers do not change with ... ...

    Abstract Background Type 2 diabetes (T2D) is a heterogeneous disease for which (1) disease-causing pathways are incompletely understood and (2) subclassification may improve patient management. Unlike other biomarkers, germline genetic markers do not change with disease progression or treatment. In this paper, we test whether a germline genetic approach informed by physiology can be used to deconstruct T2D heterogeneity. First, we aimed to categorize genetic loci into groups representing likely disease mechanistic pathways. Second, we asked whether the novel clusters of genetic loci we identified have any broad clinical consequence, as assessed in four separate subsets of individuals with T2D. Methods and findings In an effort to identify mechanistic pathways driven by established T2D genetic loci, we applied Bayesian nonnegative matrix factorization (bNMF) clustering to genome-wide association study (GWAS) results for 94 independent T2D genetic variants and 47 diabetes-related traits. We identified five robust clusters of T2D loci and traits, each with distinct tissue-specific enhancer enrichment based on analysis of epigenomic data from 28 cell types. Two clusters contained variant-trait associations indicative of reduced beta cell function, differing from each other by high versus low proinsulin levels. The three other clusters displayed features of insulin resistance: obesity mediated (high body mass index [BMI] and waist circumference [WC]), "lipodystrophy-like" fat distribution (low BMI, adiponectin, and high-density lipoprotein [HDL] cholesterol, and high triglycerides), and disrupted liver lipid metabolism (low triglycerides). Increased cluster genetic risk scores were associated with distinct clinical outcomes, including increased blood pressure, coronary artery disease (CAD), and stroke. We evaluated the potential for clinical impact of these clusters in four studies containing individuals with T2D (Metabolic Syndrome in Men Study [METSIM], N = 487; Ashkenazi, N = 509; Partners Biobank, N = 2,065; UK Biobank ...
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

    Julia K. Goodrich / Moriel Singer-Berk / Rachel Son / Abigail Sveden / Jordan Wood / Eleina England / Joanne B. Cole / Ben Weisburd / Nick Watts / Lizz Caulkins / Peter Dornbos / Ryan Koesterer / Zachary Zappala / Haichen Zhang / Kristin A. Maloney / Andy Dahl / Carlos A. Aguilar-Salinas / Gil Atzmon / Francisco Barajas-Olmos /
    Nir Barzilai / John Blangero / Eric Boerwinkle / Lori L. Bonnycastle / Erwin Bottinger / Donald W. Bowden / Federico Centeno-Cruz / John C. Chambers / Nathalie Chami / Edmund Chan / Juliana Chan / Ching-Yu Cheng / Yoon Shin Cho / Cecilia Contreras-Cubas / Emilio Córdova / Adolfo Correa / Ralph A. DeFronzo / Ravindranath Duggirala / Josée Dupuis / Ma Eugenia Garay-Sevilla / Humberto García-Ortiz / Christian Gieger / Benjamin Glaser / Clicerio González-Villalpando / Ma Elena Gonzalez / Niels Grarup / Leif Groop / Myron Gross / Christopher Haiman / Sohee Han / Craig L. Hanis / Torben Hansen / Nancy L. Heard-Costa / Brian E. Henderson / Juan Manuel Malacara Hernandez / Mi Yeong Hwang / Sergio Islas-Andrade / Marit E. Jørgensen / Hyun Min Kang / Bong-Jo Kim / Young Jin Kim / Heikki A. Koistinen / Jaspal Singh Kooner / Johanna Kuusisto / Soo-Heon Kwak / Markku Laakso / Leslie Lange / Jong-Young Lee / Juyoung Lee / Donna M. Lehman / Allan Linneberg / Jianjun Liu / Ruth J. F. Loos / Valeriya Lyssenko / Ronald C. W. Ma / Angélica Martínez-Hernández / James B. Meigs / Thomas Meitinger / Elvia Mendoza-Caamal / Karen L. Mohlke / Andrew D. Morris / Alanna C. Morrison / Maggie C. Y. Ng / Peter M. Nilsson / Christopher J. O’Donnell / Lorena Orozco / Colin N. A. Palmer / Kyong Soo Park / Wendy S. Post / Oluf Pedersen / Michael Preuss / Bruce M. Psaty / Alexander P. Reiner / Cristina Revilla-Monsalve / Stephen S. Rich / Jerome I. Rotter / Danish Saleheen / Claudia Schurmann / Xueling Sim / Rob Sladek / Kerrin S. Small / Wing Yee So / Timothy D. Spector / Konstantin Strauch / Tim M. Strom / E. Shyong Tai / Claudia H. T. Tam / Yik Ying Teo / Farook Thameem / Brian Tomlinson / Russell P. Tracy / Tiinamaija Tuomi / Jaakko Tuomilehto / Teresa Tusié-Luna / Rob M. van Dam / Ramachandran S. Vasan / James G. Wilson / Daniel R. Witte / Tien-Yin Wong / AMP-T2D-GENES Consortia / Noël P. Burtt / Noah Zaitlen / Mark I. McCarthy / Michael Boehnke / Toni I. Pollin / Jason Flannick / Josep M. Mercader / Anne O’Donnell-Luria / Samantha Baxter / Jose C. Florez / Daniel G. MacArthur / Miriam S. Udler

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 15

    Abstract: Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess ... ...

    Abstract Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.
    Keywords Science ; Q
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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