29 research outputs found
Genetic effects on gene expression across human tissues
Characterization 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
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Genetic effects on gene expression across human tissues
Characterization 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
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Relation of Statin Use Prior to Admission to Severity and Recovery Among COVID-19 Inpatients.
The impact of statins, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) severity and recovery is important given their high prevalence of use among individuals at risk for severe COVID-19. We studied the association between use of statin/angiotensin-converting enzyme inhibitors/ARB in the month before hospital admission, with risk of severe outcome, and with time to severe outcome or disease recovery, among patients hospitalized for COVID-19. We performed a retrospective single-center study of all patients hospitalized at University of California San Diego Health between February 10, 2020 and June 17, 2020 (n = 170 hospitalized for COVID-19, n = 5,281 COVID-negative controls). Logistic regression and competing risks analyses were used to investigate progression to severe disease (death or intensive care unit admission), and time to discharge without severe disease. Severe disease occurred in 53% of COVID-positive inpatients. Median time from hospitalization to severe disease was 2 days; median time to recovery was 7 days. Statin use prior to admission was associated with reduced risk of severe COVID-19 (adjusted OR 0.29, 95%CI 0.11 to 0.71, p < 0.01) and faster time to recovery among those without severe disease (adjusted HR for recovery 2.69, 95%CI 1.36 to 5.33, p < 0.01). The association between statin use and severe disease was smaller in the COVID-negative cohort (p for interaction = 0.07). There was potential evidence of faster time to recovery with ARB use (adjusted HR 1.92, 95%CI 0.81 to 4.56). In conclusion, statin use during the 30 days prior to admission for COVID-19 was associated with a lower risk of developing severe COVID-19, and a faster time to recovery among patients without severe disease
Recommended from our members
Relation of Statin Use Prior to Admission to Severity and Recovery Among COVID-19 Inpatients.
The impact of statins, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) severity and recovery is important given their high prevalence of use among individuals at risk for severe COVID-19. We studied the association between use of statin/angiotensin-converting enzyme inhibitors/ARB in the month before hospital admission, with risk of severe outcome, and with time to severe outcome or disease recovery, among patients hospitalized for COVID-19. We performed a retrospective single-center study of all patients hospitalized at University of California San Diego Health between February 10, 2020 and June 17, 2020 (n = 170 hospitalized for COVID-19, n = 5,281 COVID-negative controls). Logistic regression and competing risks analyses were used to investigate progression to severe disease (death or intensive care unit admission), and time to discharge without severe disease. Severe disease occurred in 53% of COVID-positive inpatients. Median time from hospitalization to severe disease was 2 days; median time to recovery was 7 days. Statin use prior to admission was associated with reduced risk of severe COVID-19 (adjusted OR 0.29, 95%CI 0.11 to 0.71, p < 0.01) and faster time to recovery among those without severe disease (adjusted HR for recovery 2.69, 95%CI 1.36 to 5.33, p < 0.01). The association between statin use and severe disease was smaller in the COVID-negative cohort (p for interaction = 0.07). There was potential evidence of faster time to recovery with ARB use (adjusted HR 1.92, 95%CI 0.81 to 4.56). In conclusion, statin use during the 30 days prior to admission for COVID-19 was associated with a lower risk of developing severe COVID-19, and a faster time to recovery among patients without severe disease