73 research outputs found
Pulmonary Function and Blood DNA Methylation A Multiancestry Epigenome-Wide Association Meta-analysis
Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate,,0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis
Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe
A family‐centered prevention ameliorates the associations of low self‐control during childhood with employment income and poverty status in young African American adults
ELECTROPHORETIC KARYOTYPE AND GENE ASSIGNMENT TO RESOLVED CHROMOSOMES OF TRICHODERMA SPP.
Curriculum guidelines for the training of general practice residents in treating the patient with special needs
Electrophoretic karyotype and gene assignment to resolved chromosomes of Trichoderma spp.
The Art of Scenario Design
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69119/2/10.1177_003755007234004.pd
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