Biology subjects

Waggott, D.

Publications and source records attributed to Waggott, D..

4 recordsLinked to original sources

bioRxiv2017

Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank

BackgroundHand grip strength, a simple indicator of muscular strength, has been associated with a range of health conditions, including fractures, disability, cardiovascular disease and premature death risk. Twin studies have suggested a high (50-60%) heritability, but genetic determinants are largely unknown.\n\nAimsIn this study, our aim was to study genetic variation associated with muscular strength in a large sample of 334,925 individuals of European descent from the UK Biobank, and to evaluate shared genetic aetiology with and causal effects of grip strength on physical and cognitive health.\n\nMethods and ResultsIn our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength at genome-wide significance (P<5x10-8). Of these, 64 were associated (P<0.01 and consistent direction) also in the replication dataset (N=111,610). Many of the lead SNPs were located in or near genes known to have a function in developmental disorders (FTO, SLC39A8, TFAP2B, TGFA, CELF1, TCF4, BDNF, FOXP1, KIF1B, ANTXR2), and one of the most significant genes based on a gene-based analysis (ATP2A1) encodes SERCA1, the critical enzyme in calcium uptake to the sarcoplasmic reticulum, which plays a major role in muscle contraction and relaxation. Further, we demonstrated a significant enrichment of gene expression in brain-related transcripts among grip strength associations. Finally, we observed inverse genetic correlations of grip strength with cardiometabolic traits, and positive correlation with parents age of death and education; and showed that grip strength was causally related to fitness, physical activity and other indicators of frailty, including cognitive performance scores.\n\nConclusionsIn our study of over 330,000 individuals from the general population, the genetic findings for hand grip strength suggest an important role of the central nervous system in strength performance. Further, our results indicate that maintaining good muscular strength is important for physical and cognitive performance and healthy aging.

genomics↗

bioRxiv2017

BPG: Seamless, Automated and Interactive Visualization of Scientific Data

We introduce BPG, an easy-to-use framework for generating publication-quality, highly-customizable plots in the R statistical environment. This open-source package includes novel methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it ideal for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for seamless integration with computational pipelines. BPG is available at http://labs.oicr.on.ca/boutros-lab/software/bpg

bioinformatics↗

bioRxiv2016

Accuracy in wrist-worn, sensor-based measurements of heart rate and energy expenditure in a diverse cohort

BackgroundThe ability to measure activity and physiology through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown.\n\nObjectiveTo assess the accuracy of seven commercially available wrist-worn devices in estimating heart rate (HR) and energy expenditure (EE) and to propose a wearable sensor evaluation framework.\n\nMethodsWe evaluated the Apple Watch, Basis Peak, Fitbit Surge, Microsoft Band, Mio Alpha 2, PulseOn, and Samsung Gear S2. Participants wore devices while being simultaneously assessed with continuous telemetry and indirect calorimetry while sitting, walking, running, and cycling. Sixty volunteers (29 male, 31 female, age 38 {+/-} 11 years) of diverse age, height, weight, skin tone, and fitness level were selected. Error in HR and EE was computed for each subject/device/activity combination.\n\nResultsDevices reported the lowest error for cycling and the highest for walking. Device error was higher for males,greater body mass index, darker skin tone, and walking. Six of the devices achieved a median error for HR below 5% during cycling. No device achieved an error in EE below 20 percent. The Apple Watch achieved the lowest overall error in both HR and EE, while the Samsung Gear S2 reported the highest.\n\nConclusionsMost wrist-worn devices adequately measure HR in laboratory-based activities, but poorly estimate EE, suggesting caution in the use of EE measurements as part of health improvement programs. We propose reference standards for the validation of consumer health devices (http://precision.stanford.edu/).\n\nAbbreviations

bioinformatics↗

bioRxiv2016

Long-read whole genome sequencing identifies causal structural variation in a Mendelian disease

Current clinical genomics assays primarily utilize short-read sequencing (SRS), which offers high throughput, high base accuracy, and low cost per base. SRS has, however, limited ability to evaluate tandem repeats, regions with high [GC] or [AT] content, highly polymorphic regions, highly paralogous regions, and large-scale structural variants. Long-read sequencing (LRS) has complementary strengths and offers a means to discover overlooked genetic variation in patients undiagnosed by SRS. To evaluate LRS, we selected a patient who presented with multiple neoplasia and cardiac myxomata suggestive of Carney complex for whom targeted clinical gene testing and whole genome SRS were negative. Low coverage whole genome LRS was performed on the PacBio Sequel system and structural variants were called, yielding 6,971 deletions and 6,821 insertions > 50bp. Filtering for variants that are absent in an unrelated control and that overlap a coding exon of a disease gene identified three deletions and three insertions. One of these, a heterozygous 2,184 bp deletion, overlaps the first coding exon of PRKAR1A, which is implicated in autosomal dominant Carney complex. This variant was confirmed by Sanger sequencing and was classified as pathogenic using standard criteria for the interpretation of sequence variants. This first successful application of whole genome LRS to identify a pathogenic variant suggests that LRS has significant potential to identify disease-causing structural variation. We recommend larger studies to evaluate the diagnostic yield of LRS, and the development of a comprehensive catalog of common human structural variation to support future studies.

genomics↗