48 research outputs found
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Characterization of DNA methylation clock algorithms applied to diverse tissue types
Get PDFBackground: DNA methylation (DNAm) data from human samples has been leveraged to develop âepigenetic clockâ algorithms that predict age and other aging-related phenotypes. Some DNAm clocks were trained using DNAm obtained from blood cells, while other clocks were trained using data from diverse tissue/cell types. To assess how DNAm clocks perform across non-blood tissue types, we applied DNAm algorithms to DNAm data generated from 9 different human tissue types. Methods: We generated array-based DNAm measurements for 973 samples from deceased tissue donors from the GTEx (Genotype Tissue Expression) project representing nine distinct tissue types: lung, colon, prostate, ovary, breast, kidney, testis, skeletal muscle, and whole blood. For all samples, we generated DNAm clock estimates for 8 epigenetic clocks and characterized these tissue-specific clock estimates in terms of their distributions, correlations with chronological age, correlations of clock estimates between tissue types, and association with participant characteristics. Results: For each clock, the mean DNAm age estimate varied substantially across tissue types, and the mean values for the different clocks varied substantially within tissue types. For most clocks, the correlation with chronological age varied across tissue types, with blood often showing the strongest correlation. Each clock showed strong correlation across tissues, with some evidence of some residual correlation after adjusting for chronological age. In lung tissue, smoking generally had a positive association with epigenetic age. Conclusions: This work demonstrates how differences in epigenetic aging among tissue types leads to clear differences in DNAm clock characteristics across tissue types. Tissue or cell-type specific epigenetic clocks are needed to optimize predictive performance of DNAm clocks in non-blood tissues and cell types.</p
Childhood cancer incidence and survival in Thailand: A comprehensive populationâbased registry analysis, 1990â2011
Full text linkBackgroundSoutheast Asia is undergoing a transition from infectious to chronic diseases, including a dramatic increase in adult cancers. Childhood cancer research in Thailand has focused predominantly on leukemias and lymphomas or only examined children for a short period of time. This comprehensive multisite study examined childhood cancer incidence and survival rates in Thailand across all International Classification of Childhood Cancer (ICCC) groups over a 20âyear period.MethodsCancer cases diagnosed in children ages 0â19 years (n = 3574) from 1990 to 2011 were extracted from five provincial populationâbased Thai registries, covering approximately 10% of the population. Descriptive statistics of the quality of the registries were evaluated. Ageâstandardized incidence rates (ASRs) were calculated using the Segi world standard population, and relative survival was computed using the KaplanâMeier method. Changes in incidence and survival were analyzed using Joinpoint Regression and reported as annual percent changes (APC).ResultsThe ASR of all childhood cancers during the study period was 98.5 per million personâyears with 91.0 per million personâyears in 1990â2000 and 106.2 per million personâyears in 2001â2011. Incidence of all childhood cancers increased significantly (APC = 1.2%, P < 0.01). The top three cancer groups were leukemias, brain tumors, and lymphomas. The 5âyear survival for all childhood cancers significantly improved from 39.4% in 1990â2000 to 47.2% in 2001â2011 (P < 0.01).ConclusionsBoth childhood cancer incidence and survival rates have increased, suggesting improvement in the health care system as more cases are identified and treated. Analyzing childhood cancer trends in lowâ and middleâincome countries can improve understanding of cancer etiology and pediatric health care disparities.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146559/1/pbc27428_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146559/2/pbc27428.pd
Proximity to cancer rehabilitation and exercise oncology by geography, race, and socioeconomic status
Get PDFBackgroundCancer rehabilitation and exercise oncology (CR/EO) have documented benefits for people living with and beyond cancer. The authors examined proximity to CR/EO programs across the United States with respect to population density, race and ethnicity, socioeconomic status, and cancer incidence and mortality rates.MethodsThis cross-sectional study was conducted in 2022â2023. Online searches were initiated to identify CR/EO programs. Geocoding was used to obtain latitudinal and longitudinal geospatial coordinates. Demographic data were abstracted from the 2020 5-year American Community Survey. Cancer incidence and mortality data were obtained from the Centers for Disease Control and Prevention. US 2013 Rural-Urban Continuum Code (RUCC) classification was used to define counties as either urban (RUCC 1â3) or rural (RUCC 4â9). Multivariable logistic regression was used to evaluate the association between being far from a program and census-tract level factors.ResultsIn total, 2133 CR/EO programs were identified nationwide. The distance from a program increased with decreasing population density: rural tracts were 17.68 ± 0.24 miles farther from a program compared with urban tracts (p < .001). Program proximity decreased as the neighborhood deprivation index increased (p < .001). Exercise oncology programs were less common than cancer rehabilitation programs in tracts with a larger proportion of minority residents (p < .001).ConclusionsPrior research has documented that underrepresented populations have worse cancer-related symptoms and higher cancer mortality. Herein, the authors document their findings that these same populations are less likely to have proximity to CR/EO programs, which are associated with improved cancer-related symptoms and cancer mortality outcomes. To realize the positive outcomes from CR/EO programming, efforts must focus on supporting expanded programming and sustainable payment for these services
Genetic effects on gene expression across human tissues
Get PDFCharacterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas
Genetic effects on gene expression across human tissues
Get PDFCharacterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease
Disparities in Environmental Exposures and Health in Thailand: Molecular Effects of Chronic Cadmium Exposure and Trends in Childhood Leukemia
Full text linkThailand has undergone rapid social and economic changes over the past fifty years, and prevalence and mortality of disease has decreased for infectious diseases and increased for chronic diseases across the age spectrum. This dissertation focuses on identifying disparities in childhood cancer and environmental health in Thailand by examining 1) childhood leukemia incidence and survival trends from 1990-2011 in the Songkhla Province in Thailand, and 2) high cadmium (Cd) exposure among northern Thai women from Mae Sot and its effects on biologic aging and co-exposure to toxic and essential metals. The first aim utilized cancer data from the Songkhla Cancer Registry and the United States (US). Leukemia incidence and survival was significantly lower in Songkhla compared to US but incidence and survival significantly increased annually from 1990-2011 in Thailand by approximately 2%.
In the second and third aims, epigenome-wide DNA methylation and blood and urine metal biomarkers of exposure were measured in two samples of women from Mae Sot. These women were exposed to Cd, a toxic metal, after ingesting water and rice contaminated by environmental pollution from nearby zinc mining. DNA methylation is a dynamic and sensitive epigenetic marker that changes during aging and is associated with Cd exposure. Biologic age, or the physiologic age of an individual, can be estimated from a collection of a subset of these changes. A greater difference between chronologic age and biologic age may indicate accelerated aging. In Aim 2, higher Cd exposure was associated with smaller difference between biologic and chronologic age, and Cd modified methylation at some age-associated sites included in predictors of biologic age. In Aim 3 co-exposure of metals were examined in blood and urine using multivariate methods. Blood lead and urinary arsenic were also elevated in this high Cd exposed sample. Unique patterns emerged among these metals, suggesting that lead and Cd exposures were independent. Further public health interventions are necessary to address pediatric cancer incidence and survival disparities in Thailand and to study sources of exposure to other metals and other biomarkers aging within the Mae Sot population.PHDEnvironmental Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135800/1/kdemanel_1.pd
Association of AMP-Activated Protein Kinase with Risk and Progression of NonâHodgkin Lymphoma
No full textDifferences in childhood leukemia incidence and survival between Southern Thailand and the United States: a populationâbased analysis
Full text linkPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113128/1/pbc25571.pd
Childhood cancer incidence and survival in Thailand: A comprehensive population-based registry analysis, 1990â2011
No full textBackground: Southeast Asia is undergoing a transition from infectious to chronic diseases, including a dramatic increase in adult cancers. Childhood cancer research in Thailand has focused predominantly on leukemias and lymphomas or only examined children for a short period of time. This comprehensive multisite study examined childhood cancer incidence and survival rates in Thailand across all International Classification of Childhood Cancer (ICCC) groups over a 20-year period. Methods: Cancer cases diagnosed in children ages 0-19 years (n = 3574) from 1990 to 2011 were extracted from five provincial population-based Thai registries, covering approximately 10% of the population. Descriptive statistics of the quality of the registries were evaluated. Age-standardized incidence rates (ASRs) were calculated using the Segi world standard population, and relative survival was computed using the Kaplan-Meier method. Changes in incidence and survival were analyzed using Joinpoint Regression and reported as annual percent changes (APC). Results: The ASR of all childhood cancers during the study period was 98.5 per million person-years with 91.0 per million person-years in 1990â2000 and 106.2 per million person-years in 2001â2011. Incidence of all childhood cancers increased significantly (APC = 1.2%, P \u3c 0.01). The top three cancer groups were leukemias, brain tumors, and lymphomas. The 5-year survival for all childhood cancers significantly improved from 39.4% in 1990â2000 to 47.2% in 2001â2011 (P \u3c 0.01). Conclusions: Both childhood cancer incidence and survival rates have increased, suggesting improvement in the health care system as more cases are identified and treated. Analyzing childhood cancer trends in low- and middle-income countries can improve understanding of cancer etiology and pediatric health care disparities
ciseQTL_results_for_coloc
No full textThis file contains complete eQTL results for all eQTLs used in co-localization analyses. Summary results for all SNPs within 250 kb of the lead eSNP are provided
