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DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936

BackgroundThe biological mechanisms underlying frailty in older people are poorly understood. There is some evidence to suggest that DNA methylation patterns may be altered in frail individuals.MethodsParticipants were 791 people aged 70 years from the Lothian Birth Cohort 1936. DNA methylation was measured in whole blood. Biological age was estimated using two measures of DNA...

Author Correction: Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism

-Kim?Clarke Masoud?Shirali Sarah?E.?Harris Riccardo?E.?Marioni David?C.?Liewald Chloe?Fawns-Ritchie Mark?J.?Adams David?M.?Howard Cathryn?M.?Lewis Catharine?R.?Gale Andrew?M.?McIntosh Ian?J.?Deary Brad

Trajectories of inflammatory biomarkers over the eighth decade and their associations with immune cell profiles and epigenetic ageing

BackgroundEpigenetic age acceleration (an older methylation age compared to chronological age) correlates strongly with various age-related morbidities and mortality. Chronic systemic inflammation is thought to be a hallmark of ageing, but the relationship between an increased epigenetic age and this likely key phenotype of ageing has not yet been extensively investigated...

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

. Deary. Supervision: Sarah E. Harris, Catharine R. Gale, Ian J. Deary. Writing ± original draft: Saskia P. Hagenaars, Ratko Radaković, Christopher Crockford. Writing ± review & editing: Saskia P ... . Hagenaars, Ratko Radaković, Christopher Crockford, Chloe Fawns-Ritchie, Sarah E. Harris, Catharine R. Gale, Ian J. Deary. 11 / 13 12 / 13 PloS one. 2015; 10(10):e0139082. Epub 2015/10/03. https://doi.org

Identification of 55,000 Replicated DNA Methylation QTL

DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation from whole blood measured on Illumina...

Apolipoprotein E genotype does not moderate the associations of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive aging in the Lothian Birth Cohort 1936

Writing ± original draft: Zander Crook, Tom Booth. Writing ± review & editing: Zander Crook, Tom Booth, Simon R. Cox, Janie Corley, Dominika Dykiert, Paul Redmond, Alison Pattie, Adele M. Taylor, Sarah E ... . Harris, John M. Starr, Ian J. Deary. 17 / 20 20. Wang L, Zhang Z, McArdle JJ, Salthouse TA. Investigating ceiling effects in longitudinal data analysis. Multivar Behav Res. 2008; 43;476±496. 18 / 20 19

GWAS on family history of Alzheimer’s disease

for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UKRiccardo E. Marioni, Sarah E. Harris, David J. Porteous & Kathryn L ... . EvansCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UKRiccardo E. Marioni, Sarah E. Harris, Saskia P. Hagenaars, W. David Hill, Gail Davies, Catharine R

Single Nucleotide Polymorphisms Associated with Reading Ability Show Connection to Socio-Economic Outcomes

, Saskia P. Hagenaars, Simon R. Cox, William David Hill, Gail Davies, Sarah E. Harris, Ian J. Deary, David M. Evans, Nicholas G. Martin, Margaret J. Wright, and Timothy C. Bates declare that they have no

The activity and copy number of mitochondrial DNA in ovine oocytes throughout oogenesis in vivo and during oocyte maturation in vitro

Mitochondria are responsible for the production of ATP, which drives cellular metabolic and biosynthetic processes. This is the first study to quantify the mtDNA copy number across all stages of oogenesis in a large monovulatory species, it includes assessment of the activity of mitochondria in germinal vesicle (GV) and metaphase II (MII) oocytes through JC1 staining. Primordial...

Complex Variation in Measures of General Intelligence and Cognitive Change

Combining information from multiple SNPs may capture a greater amount of genetic variation than from the sum of individual SNP effects and help identifying missing heritability. Regions may capture variation from multiple common variants of small effect, multiple rare variants or a combination of both. We describe regional heritability mapping of human cognition. Measures of...

Meta-analysis of epigenome-wide association studies of cognitive abilities

Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood...

Metabolism and karyotype analysis of oocytes from patients with polycystic ovary syndrome

BACKGROUND Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances which include impaired insulin signalling and glucose metabolism in ovarian follicles. The oocyte is metabolically dependent upon its follicle environment during development, but it is unclear whether PCOS or polycystic ovarian (PCO) morphology alone affect oocyte metabolism and energy-demanding...

Alzheimer's Disease Genes Are Associated with Measures of Cognitive Ageing in the Lothian Birth Cohorts of 1921 and 1936

Alzheimer's disease patients have deficits in specific cognitive domains, and susceptibility genes for this disease may influence human cognition in nondemented individuals. To evaluate the role of Alzheimer's disease-linked genetic variation on cognition and normal cognitive ageing, we investigated two Scottish cohorts for which assessments in major cognitive domains are...

Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme

The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing...

Human Intelligence and Polymorphisms in the DNA Methyltransferase Genes Involved in Epigenetic Marking

Epigenetic mechanisms have been implicated in syndromes associated with mental impairment but little is known about the role of epigenetics in determining the normal variation in human intelligence. We measured polymorphisms in four DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L) involved in epigenetic marking and related these to childhood and adult general...

Associations between a Polymorphism in the Pleiotropic GCKR and Age-Related Phenotypes: The HALCyon Programme

Background The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such...

Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936

The APOE ε and TOMM40 rs10524523 (‘523’) variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer’s disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE...

Telomere Length and Physical Performance at Older Ages: An Individual Participant Meta-Analysis

Background Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with...

Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro

This study investigated the relationship between human preimplantation embryo metabolism and aneuploidy rates during development in vitro. One hundred and eighty-eight fresh and cryopreserved embryos from 59 patients (33.9 ± 0.6 years) were cultured for 2–5 days. The turnover of 18 amino acids was measured in spent media by high-performance liquid chromatography. Embryos were...

Genetic Basis of a Cognitive Complexity Metric

Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap...