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Steve Horvath

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https://www.readbyqxmd.com/read/29746298/perinatally-acquired-hiv-infection-accelerates-epigenetic-aging-in-south-african-adolescents
#1
Steve Horvath, Nicole Phillips, Sarah J Heany, Michael S Kobor, David Ts Lin, Landon Myer, Heather J Zar, Dan J Stein, Andrew J Levine, Jacqueline Hoare
OBJECTIVE: Recent studies demonstrate that infection with the Human Immunodeficiency Virus-1 (HIV) is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth. DESIGN: Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) Study...
May 8, 2018: AIDS
https://www.readbyqxmd.com/read/29718110/tracking-the-epigenetic-clock-across-the-human-life-course-a-meta-analysis-of-longitudinal-cohort-data
#2
Riccardo E Marioni, Matthew Suderman, Brian H Chen, Steve Horvath, Stefania Bandinelli, Tiffany Morris, Stephan Beck, Luigi Ferrucci, Nancy L Pedersen, Caroline L Relton, Ian J Deary, Sara Hägg
Background: Epigenetic clocks based on DNA methylation yield high correlations with chronological age in cross-sectional data. Due to a paucity of longitudinal data, it is not known how Δage (epigenetic age - chronological age) changes over time or if it remains constant from childhood to old age. Here, we investigate this using longitudinal DNA methylation data from five datasets, covering most of the human life course. Methods: Two measures of the epigenetic clock (Hannum and Horvath) are used to calculate Δage in the following cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) offspring (n = 986, total age-range 7-19 years, 2 waves), ALSPAC mothers (n = 982, 16-60 years, 2 waves), InCHIANTI (n = 460, 21-100 years, 2 waves), SATSA (n = 373, 48-99 years, 5 waves), Lothian Birth Cohort 1936 (n = 1,054, 70-76 years, 3 waves), and Lothian Birth Cohort 1921 (n = 476, 79-90 years, 3 waves)...
March 20, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29713391/metabolic-and-inflammatory-biomarkers-are-associated-with-epigenetic-aging-acceleration-estimates-in-the-goldn-study
#3
Marguerite R Irvin, Stella Aslibekyan, Anh Do, Degui Zhi, Bertha Hidalgo, Steven A Claas, Vinodh Srinivasasainagendra, Steve Horvath, Hemant K Tiwari, Devin M Absher, Donna K Arnett
Background: Recently, epigenetic age acceleration-or older epigenetic age in comparison to chronological age-has been robustly associated with mortality and various morbidities. However, accelerated epigenetic aging has not been widely investigated in relation to inflammatory or metabolic markers, including postprandial lipids. Methods: We estimated measures of epigenetic age acceleration in 830 Caucasian participants from the Genetics Of Lipid Lowering Drugs and diet Network (GOLDN) considering two epigenetic age calculations based on differing sets of 5'-Cytosine-phosphate-guanine-3' genomic site, derived from the Horvath and Hannum DNA methylation age calculators, respectively...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29676998/an-epigenetic-biomarker-of-aging-for-lifespan-and-healthspan
#4
Morgan E Levine, Ake T Lu, Austin Quach, Brian H Chen, Themistocles L Assimes, Stefania Bandinelli, Lifang Hou, Andrea A Baccarelli, James D Stewart, Yun Li, Eric A Whitsel, James G Wilson, Alex P Reiner, Abraham Aviv, Kurt Lohman, Yongmei Liu, Luigi Ferrucci, Steve Horvath
Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease...
April 18, 2018: Aging
https://www.readbyqxmd.com/read/29650557/sputum-proteomics-and-airway-cell-transcripts-of-current-and-ex-smokers-with-severe-asthma-in-u-biopred-an-exploratory-analysis
#5
Kentaro Takahashi, Stelios Pavlidis, Francois Ng Kee Kwong, Uruj Hoda, Christos Rossios, Kai Sun, Matthew Loza, Fred Baribaud, Pascal Chanez, Steve J Fowler, Ildiko Horvath, Paolo Montuschi, Florian Singer, Jacek Musial, Barbro Dahlen, Sven-Eric Dahlen, Norbert Krug, Thomas Sandstrom, Dominic E Shaw, Rene Lutter, Per Bakke, Louise J Fleming, Peter H Howarth, Massimo Caruso, Ana R Sousa, Julie Corfield, Charles Auffray, Bertrand De Meulder, Diane Lefaudeux, Ratko Djukanovic, Peter J Sterk, Yike Guo, Ian M Adcock, Kian Fan Chung
Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed...
May 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29643443/dna-methylation-based-biomarkers-and-the-epigenetic-clock-theory-of-ageing
#6
REVIEW
Steve Horvath, Kenneth Raj
Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course...
June 2018: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/29582356/no-reliable-gene-expression-biomarkers-of-current-or-impending-neurocognitive-impairment-in-peripheral-blood-monocytes-of-persons-living-with-hiv
#7
Austin Quach, Steve Horvath, Natasha Nemanim, Dimitrios Vatakis, Mallory D Witt, Eric N Miller, Roger Detels, Peter Langfelder, Paul Shapshak, Elyse J Singer, Andrew J Levine
Events leading to and propagating neurocognitive impairment (NCI) in HIV-1-infected (HIV+) persons are largely mediated by peripheral blood monocytes. We previously identified expression levels of individual genes and gene networks in peripheral blood monocytes that correlated with neurocognitive functioning in HIV+ adults. Here, we expand upon those findings by examining if gene expression data at baseline is predictive of change in neurocognitive functioning 2 years later. We also attempt to validate the original findings in a new sample of HIV+ patients and determine if the findings are HIV specific by including HIV-uninfected (HIV-) participants as a comparison group...
March 26, 2018: Journal of Neurovirology
https://www.readbyqxmd.com/read/29439242/shared-molecular-neuropathology-across-major-psychiatric-disorders-parallels-polygenic-overlap
#8
Michael J Gandal, Jillian R Haney, Neelroop N Parikshak, Virpi Leppa, Gokul Ramaswami, Chris Hartl, Andrew J Schork, Vivek Appadurai, Alfonso Buil, Thomas M Werge, Chunyu Liu, Kevin P White, Steve Horvath, Daniel H Geschwind
The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions...
February 9, 2018: Science
https://www.readbyqxmd.com/read/29374233/gwas-of-epigenetic-aging-rates-in-blood-reveals-a-critical-role-for-tert
#9
Ake T Lu, Luting Xue, Elias L Salfati, Brian H Chen, Luigi Ferrucci, Daniel Levy, Roby Joehanes, Joanne M Murabito, Douglas P Kiel, Pei-Chien Tsai, Idil Yet, Jordana T Bell, Massimo Mangino, Toshiko Tanaka, Allan F McRae, Riccardo E Marioni, Peter M Visscher, Naomi R Wray, Ian J Deary, Morgan E Levine, Austin Quach, Themistocles Assimes, Philip S Tsao, Devin Absher, James D Stewart, Yun Li, Alex P Reiner, Lifang Hou, Andrea A Baccarelli, Eric A Whitsel, Abraham Aviv, Alexia Cardona, Felix R Day, Nicholas J Wareham, John R B Perry, Ken K Ong, Kenneth Raj, Kathryn L Lunetta, Steve Horvath
DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA...
January 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29324753/microrna-signatures-of-endogenous-huntingtin-cag-repeat-expansion-in-mice
#10
Peter Langfelder, Fuying Gao, Nan Wang, David Howland, Seung Kwak, Thomas F Vogt, Jeffrey S Aaronson, Jim Rosinski, Giovanni Coppola, Steve Horvath, X William Yang
In Huntington's disease (HD) patients and in model organisms, messenger RNA transcriptome has been extensively studied; in contrast, comparatively little is known about expression and potential role of microRNAs. Using RNA-sequencing, we have quantified microRNA expression in four brain regions and liver, at three different ages, from an allelic series of HD model mice with increasing CAG length in the endogenous Huntingtin gene. Our analyses reveal CAG length-dependent microRNA expression changes in brain, with 159 microRNAs selectively altered in striatum, 102 in cerebellum, 51 in hippocampus, and 45 in cortex...
2018: PloS One
https://www.readbyqxmd.com/read/29235933/faster-ticking-rate-of-the-epigenetic-clock-is-associated-with-faster-pubertal-development-in-girls
#11
Alexandra M Binder, Camila Corvalan, Verónica Mericq, Ana Pereira, José Luis Santos, Steve Horvath, John Shepherd, Karin B Michels
Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function. Deviance between epigenetic age and chronological age (AgeAccel) is a predictor of health. Pubertal timing has similarly been associated with cancer risk and mortality rate among females. We examined the association between AgeAccel and pubertal timing and adolescent breast composition in the longitudinal Growth and Obesity Cohort Study. AgeAccel was estimated in whole blood using the Horvath method at breast Tanner 2 (B2) and 4 (B4)...
2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29198723/dna-methylation-analysis-identifies-loci-for-blood-pressure-regulation
#12
Melissa A Richard, Tianxiao Huan, Symen Ligthart, Rahul Gondalia, Min A Jhun, Jennifer A Brody, Marguerite R Irvin, Riccardo Marioni, Jincheng Shen, Pei-Chien Tsai, May E Montasser, Yucheng Jia, Catriona Syme, Elias L Salfati, Eric Boerwinkle, Weihua Guan, Thomas H Mosley, Jan Bressler, Alanna C Morrison, Chunyu Liu, Michael M Mendelson, André G Uitterlinden, Joyce B van Meurs, Oscar H Franco, Guosheng Zhang, Yun Li, James D Stewart, Joshua C Bis, Bruce M Psaty, Yii-Der Ida Chen, Sharon L R Kardia, Wei Zhao, Stephen T Turner, Devin Absher, Stella Aslibekyan, John M Starr, Allan F McRae, Lifang Hou, Allan C Just, Joel D Schwartz, Pantel S Vokonas, Cristina Menni, Tim D Spector, Alan Shuldiner, Coleen M Damcott, Jerome I Rotter, Walter Palmas, Yongmei Liu, Tomáš Paus, Steve Horvath, Jeffrey R O'Connell, Xiuqing Guo, Zdenka Pausova, Themistocles L Assimes, Nona Sotoodehnia, Jennifer A Smith, Donna K Arnett, Ian J Deary, Andrea A Baccarelli, Jordana T Bell, Eric Whitsel, Abbas Dehghan, Daniel Levy, Myriam Fornage
Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29120328/neuropathological-and-transcriptomic-characteristics-of-the-aged-brain
#13
Jeremy A Miller, Angela Guillozet-Bongaarts, Laura E Gibbons, Nadia Postupna, Anne Renz, Allison E Beller, Susan M Sunkin, Lydia Ng, Shannon E Rose, Kimberly A Smith, Aaron Szafer, Chris Barber, Darren Bertagnolli, Kristopher Bickley, Krissy Brouner, Shiella Caldejon, Mike Chapin, Mindy L Chua, Natalie M Coleman, Eiron Cudaback, Christine Cuhaciyan, Rachel A Dalley, Nick Dee, Tsega Desta, Tim A Dolbeare, Nadezhda I Dotson, Michael Fisher, Nathalie Gaudreault, Garrett Gee, Terri L Gilbert, Jeff Goldy, Fiona Griffin, Caroline Habel, Zeb Haradon, Nika Hejazinia, Leanne L Hellstern, Steve Horvath, Kim Howard, Robert Howard, Justin Johal, Nikolas L Jorstad, Samuel R Josephsen, Chihchau L Kuan, Florence Lai, Eric Lee, Felix Lee, Tracy Lemon, Xianwu Li, Desiree A Marshall, Jose Melchor, Shubhabrata Mukherjee, Julie Nyhus, Julie Pendergraft, Lydia Potekhina, Elizabeth Y Rha, Samantha Rice, David Rosen, Abharika Sapru, Aimee Schantz, Elaine Shen, Emily Sherfield, Shu Shi, Andy J Sodt, Nivretta Thatra, Michael Tieu, Angela M Wilson, Thomas J Montine, Eric B Larson, Amy Bernard, Paul K Crane, Richard G Ellenbogen, C Dirk Keene, Ed Lein
As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging...
November 9, 2017: ELife
https://www.readbyqxmd.com/read/29109723/inhibition-of-pro-inflammatory-and-anti-apoptotic-biomarkers-during-experimental-oral-cancer-chemoprevention-by-dietary-black-raspberries
#14
Steve Oghumu, Bruce C Casto, Jennifer Ahn-Jarvis, Logan C Weghorst, Jim Maloney, Paul Geuy, Kyle Z Horvath, Claire E Bollinger, Blake M Warner, Kurt F Summersgill, Christopher M Weghorst, Thomas J Knobloch
Oral cancer continues to be a significant public health problem worldwide. Recently conducted clinical trials demonstrate the ability of black raspberries (BRBs) to modulate biomarkers of molecular efficacy that supports a chemopreventive strategy against oral cancer. However, it is essential that a preclinical animal model of black raspberry (BRB) chemoprevention which recapitulates human oral carcinogenesis be developed, so that we can validate biomarkers and evaluate potential mechanisms of action. We therefore established the ability of BRBs to inhibit oral lesion formation in a carcinogen-induced rat oral cancer model and examined potential mechanisms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28930701/leukocyte-telomere-length-t-cell-composition-and-dna-methylation-age
#15
Brian H Chen, Cara L Carty, Masayuki Kimura, Jeremy D Kark, Wei Chen, Shengxu Li, Tao Zhang, Charles Kooperberg, Daniel Levy, Themistocles Assimes, Devin Absher, Steve Horvath, Alexander P Reiner, Abraham Aviv
Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age─ the extrinsic epigenetic age acceleration (EEAA)─ is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826)...
September 20, 2017: Aging
https://www.readbyqxmd.com/read/28851441/parkinson-s-disease-is-associated-with-dna-methylation-levels-in-human-blood-and-saliva
#16
Yu-Hsuan Chuang, Kimberly C Paul, Jeff M Bronstein, Yvette Bordelon, Steve Horvath, Beate Ritz
BACKGROUND: Several articles suggest that DNA methylation levels in blood relate to Parkinson's disease (PD) but there is a need for a large-scale study that involves suitable population based controls. The purposes of the study were: (1) to study whether PD status is associated with DNA methylation levels in blood/saliva; (2) to study whether observed associations relate to blood cell types; and (3) to characterize genome-wide significant markers ("CpGs") and clusters of CpGs (co-methylation modules) in terms of biological pathways...
August 30, 2017: Genome Medicine
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
#17
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
#18
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
#19
LETTER
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.
August 2017: Haematologica
https://www.readbyqxmd.com/read/28516910/genetic-architecture-of-epigenetic-and-neuronal-ageing-rates-in-human-brain-regions
#20
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
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