Genetic and genomic analyses on ageing and age-related complex traits

2020 ◽  
Author(s):  
Qian Zhang
Keyword(s):  
Complex Traits ◽  
Age Related ◽  
Genomic Analyses ◽  
Related Complex

Using epigenome-wide association scans of DNA methylation in age-related complex human traits

Epigenomics ◽  
2012 ◽  
Vol 4 (5) ◽  
pp. 511-526 ◽  
Author(s):  
Pei-Chien Tsai ◽  
Tim D Spector ◽  
Jordana T Bell
Keyword(s):  
Dna Methylation ◽  
Age Related ◽  
Complex Human Traits ◽  
Related Complex

scholarly journals rTASSEL: an R interface to TASSEL for association mapping of complex traits

2020 ◽  
Author(s):  
Brandon Monier ◽  
Terry M. Casstevens ◽  
Edward S. Buckler
Keyword(s):  
Complex Traits ◽  
R Package ◽  
Genomic Diversity ◽  
Reproducible Research ◽  
Data Handling ◽  
Genetics Research ◽  
Front End ◽  
Genomic Analyses ◽  
Many Core ◽  
Analytical Tools

AbstractThe need for efficient tools and applications for analyzing genomic diversity is essential for any genetics research program. One such tool, TASSEL (Trait Analysis by aSSociation, Evolution and Linkage), provides many core methods for genomic analyses. Despite its efficiency, TASSEL has limited means for reproducible research and interacting with other analytical tools. Here we present an R package rTASSEL, a front-end to connect to a variety of highly used TASSEL methods and analytical tools. The goal of this package is to create a unified scripting workflow that exploits the analytical prowess of TASSEL in conjunction with R’s popular data handling and parsing capabilities without ever having the user to switch between these two environments.

scholarly journals Genetic control of age-related gene expression and complex traits in the human brain

2017 ◽  
Author(s):  
Trevor Martin ◽  
Hunter B. Fraser
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Genetic Variants ◽  
Complex Traits ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Expression Patterns ◽  
Related Gene ◽  
Age Related

AbstractAge is the primary risk factor for many of the most common human diseases—particularly neurodegenerative diseases—yet we currently have a very limited understanding of how each individual’s genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimer’s disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that age-related changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying age-related patterns of gene expression, acting through both cis- and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.

scholarly journals An Approach to Identify New Pleiotropic Genetic Loci From Publicly Available Univariate GWAS Results

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 130-130
Author(s):  
Yury Loika ◽  
Alexander Kulminski
Keyword(s):  
Complex Traits ◽  
Metabolic Networks ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Reproductive Age ◽  
Summary Statistics ◽  
Omnibus Test ◽  
Individual Level ◽  
Age Related ◽  
Level Data

Abstract The connections between genes and multifactorial polygenic age-related traits are not trivial due to complexity of metabolic networks in an organism, which were primarily adapted to maximize fitness at reproductive age in ancient environments. Given this complexity, pleiotropy in predisposition to complex traits appears to be common phenomenon. Identifying mechanisms of pleiotropic predisposition to multiple age-related traits can be a key factor in developing strategies for extending health-span and lifespan. Correlation between complex traits may be a factor shedding light on these mechanisms. Recently, we used an omnibus test leveraging correlation between multiple age-related traits to gain insights into pleiotropic predisposition to them. The analysis using individual-level data identified large number of new pleiotropic loci and highlighted a novel phenomenon of antagonistic genetic heterogeneity, which was characterized by antagonistic directions of genetic effects for directly correlated traits. Here, we demonstrate feasibility of our approach using summary statistics from univariate genome-wide (GW) association studies (GWAS). Our analysis focused on the results for high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) from the Global Lipids Genetic Consortium, which reported 94 GW significant loci (p≤5×10-8). The traits’ correlation was estimated from the individual level data. Our approach identified 28 loci with pleiotropic predisposition to HDL-C and TG at p≤5×10-8, which did not attain univariate GW significance with either of these traits. Fifteen of them (53%) demonstrated antagonistic heterogeneity. These results show that our approach can be efficiently used in the analysis of summary statistics from published studies to identify novel pleiotropic loci.

Abstract P180: Proximity To Telomeres Or A+t Content Suffices To Project Monogenic Hypertension At An 80 % Matching Rate

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ian McKnight ◽  
Regan Raines ◽  
Hunter White ◽  
Joon W Shim
Keyword(s):  
Essential Hypertension ◽  
Stochastic Approach ◽  
Genetic Mutations ◽  
Age Related ◽  
Human Genes ◽  
Genomic Analyses ◽  
Two Factors ◽  
Degenerative Disorder ◽  
Monogenic Hypertension

Hypertension remains the single biggest risk factor contributing to the global burden of disease and mortality. Despite the prevalence of individuals with elevated blood pressure, the role of genetics in hypertension is poorly understood. We have recently demonstrated that mutations causative to the congenital disorder can be projected by a stochastic approach centered on chromosomal characteristics of proximity to telomeres (F(i)) and adenine and thymine (A+T) content (F(ii)). Here, we investigated the two chromosomal factors, F(i) and F(ii), to determine whether they are associated with high mutation rates in human genes related to essential and monogenic hypertension (MH). In essential hypertension, the mismatch of two factors and the disease as well as the correlation between the full-length size of the genes and A+T content was either unexpectedly low (~53%) or statistically insignificant. When we examined 79 genes susceptible to MH and contributing to the genetic architecture of hypertension focusing on the factor-disease matching rate, 64 of 79 genes exclusively satisfied either the F(i) or F(ii) condition. Unlike the previous study on essential hypertension, a quarter of these genes displayed high A+T content at higher than 59%. 16% of genes (13 of 79) associated with hypertension met neither F(i) nor F(ii). Furthermore, 2 of 79 genes met both F(i) and F(ii). Our analysis suggests that these two factors can explain the cause of genetic mutations in 79 loci proposed in MH roughly at an 80% rate. In comparison, these two factors proposed can only explain the cause of idiopathic disease such as essential hypertension at a rate comparable to flipping a coin (50 %). The proposed genomic analyses demonstrate an intermediate matching rate or a mediocre predictability (~75% or less) between the cause of genetic mutations and the disease in the cases of congenital heart disease, thoracic aortic aneurysm, and age-related degenerative disorder.

Spindle shaped bodies in foveolar cones of the baboon retina

1989 ◽  
Vol 47 ◽  
pp. 960-961
Author(s):  
W. Krebs ◽  
I. Krebs
Keyword(s):  
Cross Sections ◽  
Inclusion Bodies ◽  
Photoreceptor Cells ◽  
Papio Anubis ◽  
Retinal Photoreceptor ◽  
Age Related ◽  
Cone Cells ◽  
Membrane Bound ◽  
Oriented Parallel ◽  
Shaped Inclusion

Various inclusion bodies occur in vertebrate retinal photoreceptor cells. Most of them are membrane bound and associated with phagocytosis or they are age related residual bodies. We found an additional inclusion body in foveal cone cells of the baboon (Papio anubis) retina.The eyes of a 15 year old baboon were fixed by immersion in cacodylate buffered glutaraldehyde (2%)/formaldehyde (2%) as described in detail elsewhere . Pieces of retina from various locations, including the fovea, were embedded in epoxy resin such that radial or tangential sections could be cut.Spindle shaped inclusion bodies were found in the cytoplasm of only foveal cones. They were abundant in the inner segments, close to the external limiting membrane (Fig. 1). But they also occurred in the outer fibers, the perikarya, and the inner fibers (Henle’s fibers) of the cone cells. The bodies were between 0.5 and 2 μm long. Their central diameter was 0.2 to 0. 3 μm. They always were oriented parallel to the long axis of the cone cells. In longitudinal sections (Figs. 2,3) they seemed to have a fibrous skeleton that, in cross sections, turned out to consist of plate-like (Fig.4) and tubular profiles (Fig. 5).

Autophagy and ageing: implications for age-related neurodegenerative diseases

2013 ◽  
Vol 55 ◽  
pp. 119-131 ◽  
Author(s):  
Bernadette Carroll ◽  
Graeme Hewitt ◽  
Viktor I. Korolchuk
Keyword(s):  
Neurodegenerative Diseases ◽  
Energy Availability ◽  
Future Studies ◽  
Intracellular Degradation ◽  
Age Related ◽  
Autophagy Induction ◽  
Social Importance ◽  
Cellular Dysfunction ◽  
Autophagy Activity ◽  
Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

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