Author
Hooman Allayee
Other affiliations: National Health Service, University of California, University of California, Berkeley ...read more
Bio: Hooman Allayee is an academic researcher from University of Southern California. The author has contributed to research in topics: Population & Genome-wide association study. The author has an hindex of 56, co-authored 172 publications receiving 17938 citations. Previous affiliations of Hooman Allayee include National Health Service & University of California.
Papers published on a yearly basis
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TL;DR: Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
Abstract: Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
4,107 citations
Heribert Schunkert1, Inke R. König1, Sekar Kathiresan2, Muredach P. Reilly3 +163 more•Institutions (59)
TL;DR: This paper performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals.
Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
1,705 citations
Vanderbilt University1, University of Southern California2, University of Texas MD Anderson Cancer Center3, University of Wisconsin-Madison4, University of California, Los Angeles5, National Center for Genome Resources6, Portland VA Medical Center7, University of Colorado Boulder8, University of Pennsylvania9, Hannover Medical School10, Johns Hopkins University11, Oregon Health & Science University12, Cornell University13, University of Michigan14, University of Tennessee Health Science Center15, Washington University in St. Louis16, University of Toronto17, University of Memphis18, Medical Research Council19, University of Massachusetts Medical School20, Hebrew University of Jerusalem21, Université de Montréal22, Purdue University23, University of California, Davis24, Academy of Sciences of the Czech Republic25, University at Buffalo26, Emory University27, University of Cincinnati28, University of Texas Southwestern Medical Center29, New York University30, University of Groningen31, Rutgers University32, Stanford University33, Max Planck Society34, National Institutes of Health35, University of Alabama at Birmingham36, International Livestock Research Institute37, Heidelberg University38, Medical College of Wisconsin39, Icahn School of Medicine at Mount Sinai40, Oak Ridge National Laboratory41, Charité42, University of Antwerp43, RWTH Aachen University44, Paul Sabatier University45, University of California, San Francisco46, McGill University47, Pasteur Institute48, University of Western Australia49, Yale University50, University of Oxford51, Case Western Reserve University52, Roswell Park Cancer Institute53, University of Kentucky54, University of Helsinki55, University of Nebraska–Lincoln56, Harvard University57, Merck & Co.58, King's College London59, Northwestern University60, Shriners Hospitals for Children61, Thomas Jefferson University62, Novartis63, University of North Carolina at Chapel Hill64, Southern Illinois University Carbondale65, University of Rochester66
TL;DR: The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way the authors approach human health and disease.
Abstract: The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.
1,040 citations
TL;DR: It is demonstrated that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO, and it is shown that F MO3 exhibits 10-fold higher specific activity than F MO1.
756 citations
TL;DR: Variant 5-lipoxygenase genotypes identify a subpopulation with increased atherosclerosis, and the observed diet–gene interactions suggest that dietary ni6 polyunsaturated fatty acids promote, whereas marine ni3 fatty acids inhibit, leukotriene-mediated inflammation that leads to Atherosclerosis in this subpopulation.
Abstract: background Leukotrienes are inflammatory mediators generated from arachidonic acid (polyunsaturated ni6 fatty acid) by the enzyme 5-lipoxygenase Since atherosclerosis involves arterial inflammation, we hypothesized that a polymorphism in the 5-lipoxygenase gene promoter could relate to atherosclerosis in humans and that this effect could interact with the dietary intake of competing 5-lipoxygenase substrates methods We determined 5-lipoxygenase genotypes, carotid-artery intima–media thickness, and markers of inflammation in a randomly sampled cohort of 470 healthy, middle-aged women and men from the Los Angeles Atherosclerosis Study Dietary arachidonic acid and marine ni3 fatty acids (including a competing 5-lipoxygenase substrate that reduces the production of inflammatory leukotrienes) were measured with the use of six 24-hour recalls of food intake results Variant 5-lipoxygenase genotypes (lacking the common allele) were found in 60 percent of the cohort Mean ( ± SE) intima–media thickness adjusted for age, sex, height, and racial or ethnic group was increased by 80 ± 19 µm (95 percent confidence interval, 43 to 116; P<0001) among carriers of two variant alleles, as compared with carriers of the common (wild-type) allele In multivariate analysis, the increase in intima–media thickness among carriers of two variant alleles (62 µm, P<0001) was similar in this cohort to that associated with diabetes (64 µm, P=001), the strongest common cardiovascular risk factor Increased dietary arachidonic acid significantly enhanced the apparent atherogenic effect of genotype, whereas increased dietary intake of ni3 fatty acids blunted the effect Finally, the plasma level of C-reactive protein, a marker of inflammation, was increased by a factor of 2 among carriers of two variant alleles as compared with that among carriers of the common allele conclusions Variant 5-lipoxygenase genotypes identify a subpopulation with increased atherosclerosis The observed diet–gene interactions further suggest that dietary ni6 polyunsaturated fatty acids promote, whereas marine ni3 fatty acids inhibit, leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation
638 citations
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TL;DR: The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases.
Abstract: ▪ Abstract The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-κB is through interactions with an inhibitor protein called IκB. Recent evidence confirms the existence of multiple forms of IκB that appear to regulate NF-κB by distinct mechanisms. NF-κB can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-κB to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of IκB. Exciting new research has elaborated several important and unexpected findings that...
5,833 citations
TL;DR: March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.
Abstract: March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
5,739 citations
TL;DR: TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed linear model approaches for controlling population and family structure and allows for linkage disequilibrium statistics to be calculated and visualized graphically.
Abstract: Summary: Association analyses that exploit the natural diversity of a genome to map at very high resolutions are becoming increasingly important. In most studies, however, researchers must contend with the confounding effects of both population and family structure. TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed linear model approaches for controlling population and family structure. For result interpretation, the program allows for linkage disequilibrium statistics to be calculated and visualized graphically. Database browsing and data importation is facilitated by integrated middleware. Other features include analyzing insertions/deletions, calculating diversity statistics, integration of phenotypic and genotypic data, imputing missing data and calculating principal components. Availability: The TASSEL executable, user manual, example data sets and tutorial document are freely available at http://www. maizegenetics.net/tassel. The source code for TASSEL can be found at http://sourceforge.net/projects/tassel.
5,460 citations
TL;DR: Author(s): Go, Alan S; Mozaffarian, Dariush; Roger, Veronique L; Benjamin, Emelia J; Berry, Jarett D; Borden, William B; Bravata, Dawn M; Dai, Shifan; Ford, Earl S; Fox, Caroline S; Franco, Sheila; Fullerton, Heather J; Gillespie, Cathleen; Hailpern, Susan M; Heit, John A; Howard, Virginia J; Huff
Abstract: Author(s): Go, Alan S; Mozaffarian, Dariush; Roger, Veronique L; Benjamin, Emelia J; Berry, Jarett D; Borden, William B; Bravata, Dawn M; Dai, Shifan; Ford, Earl S; Fox, Caroline S; Franco, Sheila; Fullerton, Heather J; Gillespie, Cathleen; Hailpern, Susan M; Heit, John A; Howard, Virginia J; Huffman, Mark D; Kissela, Brett M; Kittner, Steven J; Lackland, Daniel T; Lichtman, Judith H; Lisabeth, Lynda D; Magid, David; Marcus, Gregory M; Marelli, Ariane; Matchar, David B; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Mussolino, Michael E; Nichol, Graham; Paynter, Nina P; Schreiner, Pamela J; Sorlie, Paul D; Stein, Joel; Turan, Tanya N; Virani, Salim S; Wong, Nathan D; Woo, Daniel; Turner, Melanie B; American Heart Association Statistics Committee and Stroke Statistics Subcommittee
5,449 citations
TL;DR: The American Heart Association's 2020 Impact Goals for Cardiovascular Diseases and Disorders are revealed, with a focus on preventing, treating, and preventing heart disease and stroke.
Abstract: Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e3
1. About These Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e7
2. American Heart Association's 2020 Impact Goals. . . . . . . . . . . . . . . . .e10
3. Cardiovascular Diseases . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .e21
4. Subclinical Atherosclerosis . . . . . . . . . . . . . . . . . . . . .e45
5. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris . . . . . . . . .e54
6. Stroke (Cerebrovascular Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . .e68
7. High Blood Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .e88
8. Congenital Cardiovascular Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97
9. Cardiomyopathy and Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . .e102
10. Disorders …
5,260 citations