Dataset Information

Genetic regulation of gene expression and splicing during a 10-year period of human aging.

ABSTRACT: BACKGROUND:Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age. RESULTS:We perform RNA sequencing in whole blood from the same individuals at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging at a population and individual level. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age. We identify 1291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories. Further, we observe a strong correlation of genetic effects on expression and splicing between the two ages, with a small subset of tested genes showing a reduction in genetic associations with expression and splicing in older age. CONCLUSIONS:These findings demonstrate that, although the transcriptome and its genetic regulation is mostly stable late in life, a small subset of genes is dynamic and is characterized by a reduction in genetic regulation, most likely due to increasing environmental variance with age.

SUBMITTER: Balliu B

PROVIDER: S-EPMC6827221 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Genetic regulation of gene expression and splicing during a 10-year period of human aging.

Balliu Brunilda B Durrant Matthew M Goede Olivia de O Abell Nathan N Li Xin X Liu Boxiang B Gloudemans Michael J MJ Cook Naomi L NL Smith Kevin S KS Knowles David A DA Pala Mauro M Cucca Francesco F Schlessinger David D Jaiswal Siddhartha S Sabatti Chiara C Lind Lars L Ingelsson Erik E Montgomery Stephen B SB

Genome biology 20191104 1

<h4>Background</h4>Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age.<h4>Results</h4>We perform RNA sequencing in whole blood from the same individuals at ages 70 and 80 to quantify how gene expression, alternative s ...[more]

PMID: 31684996

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Project description:ImportanceUnreported clinical trial results represent a violation of human rights. Oncology trials account for nearly 30% of interventional biopharmaceutical clinical studies registered on ClinicalTrials.gov and are the most numerous among all disciplines.ObjectiveTo analyze the reporting of results among all interventional oncology trials registered on ClinicalTrials.gov from 2007 through 2017.Design, setting, and participantsThis cohort study analyzed all clinical studies registered between June 1, 2007, and May 8, 2017, on ClinicalTrials.gov, the largest public clinical trial registry in the world. Trials with a recruitment status of completed or terminated and a primary completion date of on or before September 30, 2017, were selected. Data were analyzed between February 20, 2021, and February 26, 2021.Main outcomes and measuresThe main outcome was the percentage of trials that reported results either on ClinicalTrials.gov or in journal publications within 24 months of the primary completion date. Journal publication was ascertained by searching ClinicalTrials.gov for a link to the publication, PubMed using national clinical trial number, and Embase using national clinical trial number and filters.ResultsOf the 12 240 clinical trials registered in ClinicalTrials.gov, 7425 trials (60.7%; 95% CI, 60.0%-61.5%) reported results, with a 34.0% (95% CI, 30.3%-37.7%) increase in 24-month reporting rate from 2007 to 2017. Multivariable analyses confirmed that more recent trials (adjusted hazard ratio [HR], 1.11 per year increase; 95% CI, 1.10-1.13) and trials with larger sample sizes (51-100 patients: adjusted HR, 1.17 [95% CI, 1.09-1.24]; >100 patients: adjusted HR, 1.43 [95% CI, 1.33-1.54]) were more likely to report results. Terminated trials were less likely to report results compared with completed trials (adjusted HR, 0.88; 95% CI, 0.83-0.93). Compared with trials funded by industry, those funded by the National Institutes of Health were more likely to report results (adjusted HR, 1.39; 95% CI, 1.29-1.49), whereas those funded by other academic or nonprofit organizations were less likely to report results (adjusted HR, 0.66; 95% CI, 0.62-0.70). Among all 7425 trials, the results of 2807 trials (37.8%; 95% CI, 36.7%-38.9%) were posted only on ClinicalTrials.gov. These trials tended to be terminated early and to have small sample sizes (≤50 patients) compared with trials that published results in journals.Conclusions and relevanceThis study found a gradual improvement in results reporting among oncology trials over a 10-year period. Trial registries could serve as a results reporting platform for unpublished trials and as a data source of trial outcomes for future studies.

Dataset Information

Genetic regulation of gene expression and splicing during a 10-year period of human aging.

Publications

Genetic regulation of gene expression and splicing during a 10-year period of human aging.

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