scholarly journals The Medical Genome Reference Bank: a whole-genome data resource of 4,000 healthy elderly individuals. Rationale and cohort design

2018 ◽  
Author(s):  
Paul Lacaze ◽  
Mark Pinese ◽  
Warren Kaplan ◽  
Andrew Stone ◽  
Marie-Jo Brion ◽  
...  
Keyword(s):  
Large Scale ◽  
Healthy Aging ◽  
Genetic Research ◽  
Data Management System ◽  
Clinical Genetics ◽  
Whole Genome ◽  
Older Individuals ◽  
Public Health Importance ◽  
Elderly Individuals ◽  
Healthy Elderly

AbstractAllele frequency data from human reference populations is of increasing value for filtering and assignment of pathogenicity to genetic variants. Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles, and therefore particularly suitable as a reference populations for the major diseases of clinical and public health importance. However, reference studies of the healthy elderly have remained under-represented in human genetics. We have developed the Medical Genome Reference Bank (MGRB), a large-scale comprehensive whole-genome dataset of confirmed healthy elderly individuals, to provide a publicly accessible resource for health-related research, and for clinical genetics. It also represents a useful resource for studying the genetics of healthy aging. The MGRB comprises 4,000 healthy, older individuals with no reported history of cancer, cardiovascular disease or dementia, recruited from two Australian community-based cohorts. DNA derived from blood samples will be subject to whole genome sequencing. The MGRB will measure genome-wide genetic variation in 4,000 individuals, mostly of European decent, aged 60-95 years (mean age ≥ 75 years). The MGRB has committed to a policy of data sharing, employing a hierarchical data management system to maintain participant privacy and confidentiality, whilst maximizing research and clinical usage of the database. The MGRB will represent a dataset of international significance, broadly accessible to the clinical and genetic research community.

scholarly journals The Medical Genome Reference Bank: a whole-genome data resource of 4000 healthy elderly individuals. Rationale and cohort design

2018 ◽  
Vol 27 (2) ◽  
pp. 308-316 ◽  
Author(s):  
Paul Lacaze ◽  
Mark Pinese ◽  
Warren Kaplan ◽  
Andrew Stone ◽  
Marie-Jo Brion ◽  
...  
Keyword(s):  
Whole Genome ◽  
Data Resource ◽  
Elderly Individuals ◽  
Genome Data ◽  
Healthy Elderly ◽  
Cohort Design

scholarly journals The role of oxidant-antioxidant markers and resistin in metabolic syndrome elderly individuals

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110065
Author(s):  
Sylwia Dzięgielewska-Gęsiak ◽  
Karolina Wyszomirska ◽  
Edyta Fatyga ◽  
Ewa Wysocka ◽  
Małgorzata Muc-Wierzgoń
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Diastolic Blood Pressure ◽  
Plasma Lipids ◽  
Fasting Glucose ◽  
The Elderly ◽  
Older Individuals ◽  
Elderly Individuals ◽  
Healthy Elderly ◽  
Antioxidant Markers

In elderly, hormones and oxidant-antioxidant interplay are suggested to mediate biochemical balance between adipose tissue to other tissues. Thus the study attempts to explore metabolic traits, plasma resistin, and oxidant-antioxidant markers in metabolic syndrome (MetS) in comparison to non-metabolic syndrome (non-MetS) elderly individuals. A total of 541 healthy elderly Caucasians, with no acute and/or chronic disorders were invited. After taking into account inclusion/exclusion criteria’s the MetS was defined as the presence of three out of five abnormal findings and allowed to divided groups into: non-metabolic syndrome, non-MetS ( n = 25, median age 69.0 years), and newly diagnosed MetS ( n = 29; median age 70.5 years) individuals. Glucose, plasma lipids, resistin (Res), thiobarbituric acid-reacting substances (TBARS), total antioxidant status (TAS), and Cu,Zn-superoxide dismutase (SOD-1) were measured. The MetS had higher resistin than non-MetS ( p < 0.04). The linear correlation (all at p < 0.05) showed correlation for Res&triacylglycerols ( R = 0.44), and for Res&diastolic blood pressure ( R = −0.58) and for SOD-1&fasting glucose ( R = −0.34) in MetS, while in the non-MetS group fasting glucose correlates with Res ( R = 0.58) and with TAS ( R = −0.43). The multiple regression analysis (alone and in combination) showed that independently from other factors resistin correlated positively with fasting glucose (β = 0.37; R = 0.58; R 2 = 0.23; p < 0.01) in all investigated elderly participants. In the MetS resistin correlated negatively with diastolic blood pressure (β = −0.68; R = 0.80; R 2 = 0.53; p = 0.0004) moreover in that group TAS correlated negatively with HDL-C (β = −0.71; R = 0.72; R 2 = 0.37; p = 0.01). While age correlated negatively with systolic blood pressure (β = −0.60; R = 0.62; R 2 = 0.14; p = 0.03) independently from other factors in the non-MetS group. Various metabolic factors contribute to maintain serum resistin and oxidant-antioxidant balance in the elderly people in the presence or absence of MetS. Resistin may serve as a predictor of MetS in the elderly, while strong antioxidant defense interactions in older individuals may indicate good health.

scholarly journals BasePlayer: Versatile Analysis Software for Large-scale Genomic Variant Discovery

2017 ◽  
Author(s):  
Riku Katainen ◽  
Iikki Donner ◽  
Tatiana Cajuso ◽  
Eevi Kaasinen ◽  
Kimmo Palin ◽  
...  
Keyword(s):  
Large Scale ◽  
Population Genomics ◽  
Genetic Research ◽  
Genomic Research ◽  
Whole Genome ◽  
Sequencing Data ◽  
Desktop Computer ◽  
Variant Analysis ◽  
Genome Level ◽  
Ngs Data

AbstractNext-generation sequencing (NGS) is being routinely applied in life sciences and clinical practice, where the interpretation of the resulting massive data has become a critical challenge. Computational workflows, such as the Broad GATK, have been established to take raw sequencing data and produce processed data for downstream analyses. Consequently, results of these computationally demanding workflows, consisting of e.g. sequence alignment and variant calling, are increasingly being provided for customers by sequencing and bioinformatics facilities. However, downstream variant analysis, whole-genome level in particular, has been lacking a multi-purpose tool, which could take advantage of rapidly growing genomic information and integrate genetic variant, sequence, genomic annotation and regulatory (e.g. ENCODE) data interactively and in a visual fashion. Here we introduce a highly efficient and user-friendly software, BasePlayer (http://baseplayer.fi), for biological discovery in large-scale NGS data. BasePlayer enables tightly integrated comparative variant analysis and visualization of thousands of NGS data samples and millions of variants, with numerous applications in disease, regulatory and population genomics. Although BasePlayer has been designed primarily for whole-genome and exome sequencing data, it is well-suited to various study settings, diseases and organisms by supporting standard and upcoming file formats. BasePlayer transforms an ordinary desktop computer into a large-scale genomic research platform, enabling also a non-technical user to perform complex comparative variant analyses, population frequency filtering and genome level annotations under intuitive, scalable and highly-responsive user interface to facilitate everyday genetic research as well as the search of novel discoveries.

scholarly journals Transcriptomic changes highly similar to Alzheimer's disease are observed in a subpopulation of individuals during normal brain aging

2021 ◽  
Author(s):  
Shouneng Peng ◽  
Lu Zeng ◽  
Jean-vianney Haure-mirande ◽  
Minghui Wang ◽  
Derek M. Huffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Healthy Aging ◽  
Brain Aging ◽  
Late Onset ◽  
Normal Aging ◽  
Normal Brain ◽  
Older Individuals

Aging is a major risk factor for late-onset Alzheimer's disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examine multiple large-scale human brain transcriptomic data from both normal aging and LOAD to understand the molecular interconnection between aging and LOAD. We find that shared gene expression changes between aging and LOAD are mostly seen in the hippocampus and several cortical regions. In the hippocampus, phosphoprotein, alternative splicing and cytoskeleton are the commonly dysregulated biological pathways in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also find that normal aging brains from relatively young donors (45-70 years old) cluster into subgroups and some subgroups show gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptome data from older individuals (>70 years), we find that samples from cognitive normal older individuals cluster with the "healthy aging" subgroup while AD samples mainly cluster with the AD similar subgroups. This implies that individuals in the healthy aging subgroup will likely remain cognitive normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitive normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the "normal brain aging" in a subgroup of individuals in their 40s-60s to identify the very early events in LOAD development.

scholarly journals The Medical Genome Reference Bank: Whole genomes and phenotype of 2,570 healthy elderly

2018 ◽  
Author(s):  
Mark Pinese ◽  
Paul Lacaze ◽  
Emma M. Rath ◽  
Andrew Stone ◽  
Marie-Jo Brion ◽  
...  
Keyword(s):  
Association Studies ◽  
Healthy Ageing ◽  
Whole Genome Sequence ◽  
Clinical Genetics ◽  
Whole Genome ◽  
Uk Biobank ◽  
Healthy Elderly ◽  
Age Related ◽  
Whole Genomes ◽  
The Uk

SummaryPopulation health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2,570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analysed the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. Individuals in the MGRB had fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK BioBank cohorts, consistent with risk depletion. Pervasive age-related somatic changes were correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. This research has been conducted using the UK Biobank Resource under Application Number 17984.

scholarly journals Epigenetic aging of classical monocytes from healthy individuals

2020 ◽  
Author(s):  
Irina Shchukina ◽  
Juhi Bagaitkar ◽  
Oleg Shpynov ◽  
Ekaterina Loginicheva ◽  
Sofia Porter ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Large Scale ◽  
Healthy Aging ◽  
Cpg Islands ◽  
Blood Protein ◽  
Older Individuals ◽  
Total Blood ◽  
Age Related ◽  
The Impact ◽  
Classical Monocytes

ABSTRACTThe impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older individuals (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Optimized ultra-low-input ChIP-seq (ULI-ChIP-seq) data acquisition and analysis pipelines applied to 5 chromatin marks for each individual revealed lack of large-scale age-associated changes in chromatin modifications and allowed us to link hypo- and hypermethylated DMRs to distinct chromatin modification patterns. Specifically, hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with normal pattern of expression. Furthermore, hypo- and hypermethylated DMRs followed distinct functional and genetic association patterns. Hypomethylation events were associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells. Furthermore, these locations were also enriched in genetic regions associated by GWAS with asthma, total blood protein, hemoglobin levels and MS. On the other side, acceleration of epigenetic age in HIV and asthma stems only from changes in hypermethylated DMRs but not from hypomethylated loci.

Psychophysiological Responses to Stress Related to Anxiety in Healthy Aging

2019 ◽  
Vol 33 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Roberta Adorni ◽  
Agostino Brugnera ◽  
Alessia Gatti ◽  
Giorgio A. Tasca ◽  
Kaoru Sakatani ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Near Infrared ◽  
Response Times ◽  
Cognitive Resources ◽  
Stressful Condition ◽  
Healthy Elderly ◽  
Situational Stress ◽  
Anxiety Response ◽  
Nirs Signal ◽  
Psychophysiological Correlates

Abstract. The aim of the study was to explore the effects of situational stress and anxiety in a group of healthy elderly, both in terms of psychophysiological correlates and cognitive performance. Eighteen participants ( Mage = 70 ± 6.3; range 60–85) were assessed for anxiety and were instructed to perform a computerized math task, under both a stressful and a control condition, while near-infrared spectroscopy (NIRS) signal and electrocardiography (ECG) were recorded. NIRS results evidenced an increased activation of right PFC during the entire procedure, even if effect sizes between left and right channels were larger during the experimental condition. The amount of right activation during the stressful condition was positively correlated with anxiety. Response times (RTs) were slower in more anxious than in less anxious individuals, both during the control and stressful conditions. Accuracy was lower in more anxious than in less anxious individuals, only during the stressful condition. Moreover, heart rate (HR) was not modulated by situational stress, nor by anxiety. Overall, the present study suggests that in healthy elderly, anxiety level has a significant impact on cerebral responses, and both on the amount of cognitive resources and the quality of performance in stressful situations.

0306 Exploring the feasibility of using copy number variants as genetic markers through large-scale whole genome sequencing experiments

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 146-146
Author(s):  
D. M. Bickhart ◽  
L. Xu ◽  
J. L. Hutchison ◽  
J. B. Cole ◽  
D. J. Null ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genetic Markers ◽  
Genome Sequencing ◽  
Copy Number ◽  
Large Scale ◽  
Copy Number Variants ◽  
Whole Genome

Age Advantages of Emotional Experience during the COVID-19 Pandemic are Robust, but Diminished Compared to Pre-pandemic Conditions

2020 ◽  
Author(s):  
Rui Sun ◽  
Disa Sauter
Keyword(s):  
Older Adults ◽  
Large Scale ◽  
Negative Emotion ◽  
Emotional Experience ◽  
Negative Emotions ◽  
Older Individuals ◽  
Selection Strategies ◽  
Scale Test ◽  
Prolonged Stress

Getting old is generally seen as unappealing, yet aging confers considerable advantages in several psychological domains (North &amp; Fiske, 2015). In particular, older adults are better off emotionally than younger adults, with aging associated with the so-called “age advantages,” that is, more positive and less negative emotional experiences (Carstensen et al., 2011). Although the age advantages are well established, it is less clear whether they occur under conditions of prolonged stress. In a recent study, Carstensen et al (2020) demonstrated that the age advantages persist during the COVID-19 pandemic, suggesting that older adults are able to utilise cognitive and behavioural strategies to ameliorate even sustained stress. Here, we build on Carstensen and colleagues’ work with two studies. In Study 1, we provide a large-scale test of the robustness of Carstensen and colleagues’ finding that older individuals experience more positive and less negative emotions during the COVID-19 pandemic. We measured positive and negative emotions along with age information in 23,629 participants in 63 countries in April-May 2020. In Study 2, we provide a comparison of the age advantages using representative samples collected before and during the COVID-19 pandemic. We demonstrate that older people experience less negative emotion than younger people during the prolonged stress of the COVID-19 pandemic. However, the advantage of older adults was diminished during the pandemic, pointing to a likely role of older adults use of situation selection strategies (Charles, 2010).

Sign in / Sign up

Export Citation Format

Share Document