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Steve Horvath

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https://www.readbyqxmd.com/read/28611571/exosomes-and-homeostatic-synaptic-plasticity-are-linked-to-each-other-and-to-huntington-s-parkinson-s-and-other-neurodegenerative-diseases-by-database-enabled-analyses-of-comprehensively-curated-datasets
#1
James K T Wang, Peter Langfelder, Steve Horvath, Michael J Palazzolo
Huntington's disease (HD) is a progressive and autosomal dominant neurodegeneration caused by CAG expansion in the huntingtin gene (HTT), but the pathophysiological mechanism of mutant HTT (mHTT) remains unclear. To study HD using systems biological methodologies on all published data, we undertook the first comprehensive curation of two key PubMed HD datasets: perturbation genes that impact mHTT-driven endpoints and therefore are putatively linked causally to pathogenic mechanisms, and the protein interactome of HTT that reflects its biology...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28556790/dna-methylation-profiling-of-human-prefrontal-cortex-neurons-in-heroin-users-shows-significant-difference-between-genomic-contexts-of-hyper-and-hypomethylation-and-a-younger-epigenetic-age
#2
Alexey Kozlenkov, Andrew E Jaffe, Alisa Timashpolsky, Pasha Apontes, Sergei Rudchenko, Mihaela Barbu, William Byne, Yasmin L Hurd, Steve Horvath, Stella Dracheva
We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm) in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC) of heroin users who died from heroin overdose (N = 37), suicide completers (N = 22) with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28). We identified 1298 differentially methylated CpG sites (DMSs) between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0...
May 30, 2017: Genes
https://www.readbyqxmd.com/read/28550187/dynamics-of-epigenetic-age-following-hematopoietic-stem-cell-transplantation
#3
Friedrich Stölzel, Mario Brosch, Steve Horvath, Michael Kramer, Christian Thiede, Malte von Bonin, Ole Ammerpohl, Moritz Middeke, Johannes Schetelig, Gerhard Ehninger, Jochen Hampe, Martin Bornhäuser
No abstract text is available yet for this article.
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28516910/genetic-architecture-of-epigenetic-and-neuronal-ageing-rates-in-human-brain-regions
#4
Ake T Lu, Eilis Hannon, Morgan E Levine, Eileen M Crimmins, Katie Lunnon, Jonathan Mill, Daniel H Geschwind, Steve Horvath
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10(-20))...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28377537/accelerated-epigenetic-aging-in-werner-syndrome
#5
Anna Maierhofer, Julia Flunkert, Junko Oshima, George M Martin, Thomas Haaf, Steve Horvath
Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0...
April 2017: Aging
https://www.readbyqxmd.com/read/28373601/an-epigenetic-aging-clock-for-dogs-and-wolves
#6
Michael J Thompson, Bridgett vonHoldt, Steve Horvath, Matteo Pellegrini
Several articles describe highly accurate age estimation methods based on human DNA-methylation data. It is not yet known whether similar epigenetic aging clocks can be developed based on blood methylation data from canids. Using Reduced Representation Bisulfite Sequencing, we assessed blood DNA-methylation data from 46 domesticated dogs (Canis familiaris) and 62 wild gray wolves (C. lupus). By regressing chronological dog age on the resulting CpGs, we defined highly accurate multivariate age estimators for dogs (based on 41 CpGs), wolves (67 CpGs), and both combined (115 CpGs)...
March 28, 2017: Aging
https://www.readbyqxmd.com/read/28364215/dna-methylation-age-is-elevated-in-breast-tissue-of-healthy-women
#7
Mary E Sehl, Jill E Henry, Anna Maria Storniolo, Patricia A Ganz, Steve Horvath
BACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference...
March 31, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28259012/dna-methylome-analysis-identifies-accelerated-epigenetic-ageing-associated-with-postmenopausal-breast-cancer-susceptibility
#8
Srikant Ambatipudi, Steve Horvath, Flavie Perrier, Cyrille Cuenin, Hector Hernandez-Vargas, Florence Le Calvez-Kelm, Geoffroy Durand, Graham Byrnes, Pietro Ferrari, Liacine Bouaoun, Athena Sklias, Véronique Chajes, Kim Overvad, Gianluca Severi, Laura Baglietto, Françoise Clavel-Chapelon, Rudolf Kaaks, Myrto Barrdahl, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Androniki Naska, Giovanna Masala, Claudia Agnoli, Silvia Polidoro, Rosario Tumino, Salvatore Panico, Martijn Dollé, Petra H M Peeters, N Charlotte Onland-Moret, Torkjel M Sandanger, Therese H Nøst, Elisabete Weiderpass, J Ramón Quirós, Antonio Agudo, Miguel Rodriguez-Barranco, José María Huerta Castaño, Aurelio Barricarte, Ander Matheu Fernández, Ruth C Travis, Paolo Vineis, David C Muller, Elio Riboli, Marc Gunter, Isabelle Romieu, Zdenko Herceg
AIM OF THE STUDY: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. METHODS: Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples...
April 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28237978/longitudinal-study-of-surrogate-aging-measures-during-human-immunodeficiency-virus-seroconversion
#9
Janice M Leung, Nick Fishbane, Meaghan Jones, Alexander Morin, Stella Xu, Joseph Cy Liu, Julie MacIsaac, M-J Milloy, Kanna Hayashi, Julio Montaner, Steve Horvath, Michael Kobor, Don D Sin, P Richard Harrigan, S F Paul Man
Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform...
February 23, 2017: Aging
https://www.readbyqxmd.com/read/28231077/association-of-genetic-variation-in-the-tachykinin-receptor-3-locus-with-hot-flashes-and-night-sweats-in-the-women-s-health-initiative-study
#10
Carolyn J Crandall, JoAnn E Manson, Chancellor Hohensee, Steve Horvath, Jean Wactawski-Wende, Erin S LeBlanc, Mara Z Vitolins, Rami Nassir, Janet S Sinsheimer
OBJECTIVE: Vasomotor symptoms (VMS, ie, hot flashes or night sweats) are reported by many, but not all, women. The extent to which VMS are genetically determined is unknown. We evaluated the relationship of genetic variation and VMS. METHODS: In this observational study, we accessed data from three genome-wide association studies (GWAS) (SNP Health Association Resource cohort [SHARe], WHI Memory Study cohort [WHIMS+], and Genome-Wide Association Studies of Treatment Response in Randomized Clinical Trials [GARNET] studies, total n = 17,695) of European American, African American, and Hispanic American postmenopausal women aged 50 to 79 years at baseline in the Women's Health Initiative Study...
March 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28198702/epigenetic-clock-analysis-of-diet-exercise-education-and-lifestyle-factors
#11
Austin Quach, Morgan E Levine, Toshiko Tanaka, Ake T Lu, Brian H Chen, Luigi Ferrucci, Beate Ritz, Stefania Bandinelli, Marian L Neuhouser, Jeannette M Beasley, Linda Snetselaar, Robert B Wallace, Philip S Tsao, Devin Absher, Themistocles L Assimes, James D Stewart, Yun Li, Lifang Hou, Andrea A Baccarelli, Eric A Whitsel, Steve Horvath
Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions, and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti...
February 14, 2017: Aging
https://www.readbyqxmd.com/read/28198392/coffee-consumption-is-associated-with-dna-methylation-levels-of-human-blood
#12
Yu-Hsuan Chuang, Austin Quach, Devin Absher, Themistocles Assimes, Steve Horvath, Beate Ritz
Beneficial health effects have been attributed to coffee consumption, but it is not yet known whether epigenetics may have a role in this process. Here we associate epigenome-wide DNA methylation levels to habitual coffee consumption from two studies with blood (2100 and 215 participants), and one with saliva samples (256 participants). Adjusting for age, gender, and blood cell composition, one CpG (cg21566642 near ALPPL2) surpassed genome-wide significance (P=3.7 × 10(-10)) and from among 10 additional CpGs significant at P≤5...
May 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28174738/microgeographic-proteomic-networks-of-the-human-colonic-mucosa-and-their-association-with-inflammatory-bowel-disease
#13
Xiaoxiao Li, James LeBlanc, David Elashoff, Ian McHardy, Maomeng Tong, Bennett Roth, Andrew Ippoliti, Gildardo Barron, Dermot McGovern, Keely McDonald, Rodney Newberry, Thomas Graeber, Steve Horvath, Lee Goodglick, Jonathan Braun
BACKGROUND & AIMS: Interactions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosal-luminal interface to study the disease-related biology of the human colonic mucosa. METHODS: We recruited a discovery cohort of 51 IBD and non-IBD subjects endoscopically sampled by mucosal lavage at 6 colonic regions, and a validation cohort of 38 no-IBD subjects...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28089957/the-epigenetic-clock-and-physical-development-during-childhood-and-adolescence-longitudinal-analysis-from-a-uk-birth-cohort
#14
Andrew J Simpkin, Laura D Howe, Kate Tilling, Tom R Gaunt, Oliver Lyttleton, Wendy L McArdle, Susan M Ring, Steve Horvath, George Davey Smith, Caroline L Relton
Background: Statistical models that use an individual's DNA methylation levels to estimate their age (known as epigenetic clocks) have recently been developed, with 96% correlation found between epigenetic and chronological age. We postulate that differences between estimated and actual age [age acceleration (AA)] can be used as a measure of developmental age in early life. Methods: We obtained DNA methylation measures at three time points (birth, age 7 years and age 17 years) in 1018 children from the Avon Longitudinal Study of Parents and Children (ALSPAC)...
April 1, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28058013/aging-related-methylation-influences-the-gene-expression-of-key-control-genes-in-colorectal-cancer-and-adenoma
#15
Orsolya Galamb, Alexandra Kalmár, Barbara Kinga Barták, Árpád V Patai, Katalin Leiszter, Bálint Péterfia, Barnabás Wichmann, Gábor Valcz, Gábor Veres, Zsolt Tulassay, Béla Molnár
AIM: To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS: In silico DNA methylation analysis of 353 epigenetic clock CpG sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer (CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated age-related genes, secreted frizzled related protein 1 (SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting (MS-HRM) analysis...
December 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27955697/dna-methylation-signatures-of-chronic-low-grade-inflammation-are-associated-with-complex-diseases
#16
Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M Mendelson, Karen N Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L Waite, Roby Joehanes, Weihua Guan, Jennifer A Brody, Cathy Elks, Riccardo Marioni, Min A Jhun, Golareh Agha, Jan Bressler, Cavin K Ward-Caviness, Brian H Chen, Tianxiao Huan, Kelly Bakulski, Elias L Salfati, Giovanni Fiorito, Simone Wahl, Katharina Schramm, Jin Sha, Dena G Hernandez, Allan C Just, Jennifer A Smith, Nona Sotoodehnia, Luke C Pilling, James S Pankow, Phil S Tsao, Chunyu Liu, Wei Zhao, Simonetta Guarrera, Vasiliki J Michopoulos, Alicia K Smith, Marjolein J Peters, David Melzer, Pantel Vokonas, Myriam Fornage, Holger Prokisch, Joshua C Bis, Audrey Y Chu, Christian Herder, Harald Grallert, Chen Yao, Sonia Shah, Allan F McRae, Honghuang Lin, Steve Horvath, Daniele Fallin, Albert Hofman, Nicholas J Wareham, Kerri L Wiggins, Andrew P Feinberg, John M Starr, Peter M Visscher, Joanne M Murabito, Sharon L R Kardia, Devin M Absher, Elisabeth B Binder, Andrew B Singleton, Stefania Bandinelli, Annette Peters, Melanie Waldenberger, Giuseppe Matullo, Joel D Schwartz, Ellen W Demerath, André G Uitterlinden, Joyce B J van Meurs, Oscar H Franco, Yii-Der Ida Chen, Daniel Levy, Stephen T Turner, Ian J Deary, Kerry J Ressler, Josée Dupuis, Luigi Ferrucci, Ken K Ong, Themistocles L Assimes, Eric Boerwinkle, Wolfgang Koenig, Donna K Arnett, Andrea A Baccarelli, Emelia J Benjamin, Abbas Dehghan
BACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111)...
December 12, 2016: Genome Biology
https://www.readbyqxmd.com/read/27926864/low-cd38-identifies-progenitor-like-inflammation-associated-luminal-cells-that-can-initiate-human-prostate-cancer-and-predict-poor-outcome
#17
Xian Liu, Tristan R Grogan, Haley Hieronymus, Takao Hashimoto, Jack Mottahedeh, Donghui Cheng, Lijun Zhang, Kevin Huang, Tanya Stoyanova, Jung Wook Park, Ruzanna O Shkhyan, Behdokht Nowroozizadeh, Matthew B Rettig, Charles L Sawyers, David Elashoff, Steve Horvath, Jiaoti Huang, Owen N Witte, Andrew S Goldstein
Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38(lo) luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38(lo) luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27919067/genome-wide-changes-in-lncrna-splicing-and-regional-gene-expression-patterns-in-autism
#18
Neelroop N Parikshak, Vivek Swarup, T Grant Belgard, Manuel Irimia, Gokul Ramaswami, Michael J Gandal, Christopher Hartl, Virpi Leppa, Luis de la Torre Ubieta, Jerry Huang, Jennifer K Lowe, Benjamin J Blencowe, Steve Horvath, Daniel H Geschwind
Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood. Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge, we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27717399/an-epigenetic-clock-for-gestational-age-at-birth-based-on-blood-methylation-data
#19
Anna K Knight, Jeffrey M Craig, Christiane Theda, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, Christine S Hansen, Mads V Hollegaard, David M Hougaard, Preben B Mortensen, Shantel M Weinsheimer, Thomas M Werge, Patricia A Brennan, Joseph F Cubells, D Jeffrey Newport, Zachary N Stowe, Jeanie L Y Cheong, Philippa Dalach, Lex W Doyle, Yuk J Loke, Andrea A Baccarelli, Allan C Just, Robert O Wright, Mara M Téllez-Rojo, Katherine Svensson, Letizia Trevisi, Elizabeth M Kennedy, Elisabeth B Binder, Stella Iurato, Darina Czamara, Katri Räikkönen, Jari M T Lahti, Anu-Katriina Pesonen, Eero Kajantie, Pia M Villa, Hannele Laivuori, Esa Hämäläinen, Hea Jin Park, Lynn B Bailey, Sasha E Parets, Varun Kilaru, Ramkumar Menon, Steve Horvath, Nicole R Bush, Kaja Z LeWinn, Frances A Tylavsky, Karen N Conneely, Alicia K Smith
BACKGROUND: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. RESULTS: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples...
October 7, 2016: Genome Biology
https://www.readbyqxmd.com/read/27702440/epigenetic-aging-and-immune-senescence-in-women-with-insomnia-symptoms-findings-from-the-women-s-health-initiative-study
#20
Judith E Carroll, Michael R Irwin, Morgan Levine, Teresa E Seeman, Devin Absher, Themistocles Assimes, Steve Horvath
BACKGROUND: Insomnia symptoms are associated with vulnerability to age-related morbidity and mortality. Cross-sectional data suggest that accelerated biological aging may be a mechanism through which sleep influences risk. A novel method for determining age acceleration using epigenetic methylation to DNA has demonstrated predictive utility as an epigenetic clock and prognostic of age-related morbidity and mortality. METHODS: We examined the association of epigenetic age and immune cell aging with sleep in the Women's Health Initiative study (N = 2078; mean 64...
January 15, 2017: Biological Psychiatry
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