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https://www.readbyqxmd.com/read/28748955/bayesian-association-scan-reveals-loci-associated-with-human-lifespan-and-linked-biomarkers
#1
Aaron F McDaid, Peter K Joshi, Eleonora Porcu, Andrea Komljenovic, Hao Li, Vincenzo Sorrentino, Maria Litovchenko, Roel P J Bevers, Sina Rüeger, Alexandre Reymond, Murielle Bochud, Bart Deplancke, Robert W Williams, Marc Robinson-Rechavi, Fred Paccaud, Valentin Rousson, Johan Auwerx, James F Wilson, Zoltán Kutalik
The enormous variation in human lifespan is in part due to a myriad of sequence variants, only a few of which have been revealed to date. Since many life-shortening events are related to diseases, we developed a Mendelian randomization-based method combining 58 disease-related GWA studies to derive longevity priors for all HapMap SNPs. A Bayesian association scan, informed by these priors, for parental age of death in the UK Biobank study (n=116,279) revealed 16 independent SNPs with significant Bayes factor at a 5% false discovery rate (FDR)...
July 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28747529/detection-and-quantification-of-inbreeding-depression-for-complex-traits-from-snp-data
#2
Loic Yengo, Zhihong Zhu, Naomi R Wray, Bruce S Weir, Jian Yang, Matthew R Robinson, Peter M Visscher
Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS)...
July 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28746715/identification-of-genetic-loci-jointly-influencing-schizophrenia-risk-and-the-cognitive-traits-of-verbal-numerical-reasoning-reaction-time-and-general-cognitive-function
#3
Olav B Smeland, Oleksandr Frei, Karolina Kauppi, W David Hill, Wen Li, Yunpeng Wang, Florian Krull, Francesco Bettella, Jon A Eriksen, Aree Witoelar, Gail Davies, Chun C Fan, Wesley K Thompson, Max Lam, Todd Lencz, Chi-Hua Chen, Torill Ueland, Erik G Jönsson, Srdjan Djurovic, Ian J Deary, Anders M Dale, Ole A Andreassen
Importance: Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction...
July 26, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28736445/dietary-fat-and-total-energy-intake-modifies-the-effect-of-genetic-profile-risk-score-on-obesity-evidence-from-48-170-uk-biobank-participants
#4
C A Celis-Morales, D M Lyall, S Gray, L Steell, J Anderson, S Iliodromiti, P Welsh, Y Guo, F Petermann, D F Mackay, M E S Bailey, J Pell, J M R Gill, N Sattar
BACKGROUND: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. METHODS: This study included cross-sectional data from 48 170 white European adults, aged 37-73 years, participating on the UK Biobank...
July 24, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28733474/persons-with-chronic-widespread-pain-experience-excess-mortality-longitudinal-results-from-uk-biobank-and-meta-analysis
#5
Gary J Macfarlane, Maxwell S Barnish, Gareth T Jones
OBJECTIVE: It is uncertain whether persons with chronic widespread pain (CWP) experience premature mortality. Using the largest study conducted, we determine whether such a relationship exists, estimate its magnitude and establish what factors mediate any relationship. METHODS: UK Biobank, a cohort study of 0.5 million people aged 40-69 years, recruited throughout Great Britain in 2006-2010. Participants reporting 'pain all over the body' for >3 months were compared with persons without chronic pain...
July 21, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28727628/replication-confirms-the-association-of-loci-in-foxe1-pde8b-capzb-and-pde10a-with-thyroid-traits-a-genetics-of-diabetes-audit-and-research-tayside-study
#6
Enrique Soto-Pedre, Moneeza K Siddiqui, Alex S Doney, Colin N A Palmer, Ewan R Pearson, Graham P Leese
OBJECTIVE: Replication of associations in genome-wide association studies is desirable to ensure that such signals are potentially clinically meaningful. This study aimed to replicate associations of selected single-nucleotide polymorphisms (SNPs) with hypothyroidism and serum thyroid-stimulating hormone (TSH) using electronic medical records (EMRs). PATIENTS AND METHODS: A cross-sectional study was carried out among patients of European Caucasian ethnicity from the Genetics of Diabetes Audit and Research Tayside recruited in Tayside (Scotland, UK)...
July 19, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28717197/subcortical-volume-and-white-matter-integrity-abnormalities-in-major-depressive-disorder-findings-from-uk-biobank-imaging-data
#7
Xueyi Shen, Lianne M Reus, Simon R Cox, Mark J Adams, David C Liewald, Mark E Bastin, Daniel J Smith, Ian J Deary, Heather C Whalley, Andrew M McIntosh
Previous reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, scanners and imaging sequences may, however, obscure further anatomical differences. In this study, we tested for differences in subcortical grey matter volume (n = 1157) and white matter integrity (n = 1089) between depressed individuals and controls in the subset of 8590 UK Biobank Imaging study participants who had undergone depression assessments...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714975/association-analyses-based-on-false-discovery-rate-implicate-new-loci-for-coronary-artery-disease
#8
Christopher P Nelson, Anuj Goel, Adam S Butterworth, Stavroula Kanoni, Tom R Webb, Eirini Marouli, Lingyao Zeng, Ioanna Ntalla, Florence Y Lai, Jemma C Hopewell, Olga Giannakopoulou, Tao Jiang, Stephen E Hamby, Emanuele Di Angelantonio, Themistocles L Assimes, Erwin P Bottinger, John C Chambers, Robert Clarke, Colin N A Palmer, Richard M Cubbon, Patrick Ellinor, Raili Ermel, Evangelos Evangelou, Paul W Franks, Christopher Grace, Dongfeng Gu, Aroon D Hingorani, Joanna M M Howson, Erik Ingelsson, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Terho Lehtimäki, Xiangfeng Lu, Yingchang Lu, Winfried März, Ruth McPherson, Andres Metspalu, Mar Pujades-Rodriguez, Arno Ruusalepp, Eric E Schadt, Amand F Schmidt, Michael J Sweeting, Pierre A Zalloua, Kamal AlGhalayini, Bernard D Keavney, Jaspal S Kooner, Ruth J F Loos, Riyaz S Patel, Martin K Rutter, Maciej Tomaszewski, Ioanna Tzoulaki, Eleftheria Zeggini, Jeanette Erdmann, George Dedoussis, Johan L M Björkegren, Heribert Schunkert, Martin Farrall, John Danesh, Nilesh J Samani, Hugh Watkins, Panos Deloukas
Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10(-8)) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS...
July 17, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28714974/genetic-analysis-in-uk-biobank-links-insulin-resistance-and-transendothelial-migration-pathways-to-coronary-artery-disease
#9
Derek Klarin, Qiuyu Martin Zhu, Connor A Emdin, Mark Chaffin, Steven Horner, Brian J McMillan, Alison Leed, Michael E Weale, Chris C A Spencer, François Aguet, Ayellet V Segrè, Kristin G Ardlie, Amit V Khera, Virendar K Kaushik, Pradeep Natarajan, Sekar Kathiresan
UK Biobank is among the world's largest repositories for phenotypic and genotypic information in individuals of European ancestry. We performed a genome-wide association study in UK Biobank testing ∼9 million DNA sequence variants for association with coronary artery disease (4,831 cases and 115,455 controls) and carried out meta-analysis with previously published results. We identified 15 new loci, bringing the total number of loci associated with coronary artery disease to 95 at the time of analysis. Phenome-wide association scanning showed that CCDC92 likely affects coronary artery disease through insulin resistance pathways, whereas experimental analysis suggests that ARHGEF26 influences the transendothelial migration of leukocytes...
July 17, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28712995/investigations-into-within-and-between-subject-resting-state-amplitude-variations
#10
Janine Bijsterbosch, Samuel Harrison, Eugene Duff, Fidel Alfaro-Almagro, Mark Woolrich, Stephen Smith
The amplitudes of spontaneous fluctuations in brain activity may be a significant source of within-subject and between-subject variability, and this variability is likely to be carried through into functional connectivity (FC) estimates (whether directly or indirectly). Therefore, improving our understanding of amplitude fluctuations over the course of a resting state scan and variation in amplitude across individuals is of great relevance to the interpretation of FC findings. We investigate resting state amplitudes in two large-scale studies (HCP and UK Biobank), with the aim of determining between-subject and within-subject variability...
July 13, 2017: NeuroImage
https://www.readbyqxmd.com/read/28706094/ventilatory-function-as-a-predictor-of-mortality-in-lifelong-non-smokers-evidence-from-large-british-cohort-studies
#11
Ramyani P Gupta, David P Strachan
BACKGROUND: Reduced ventilatory function is an established predictor of all-cause mortality in general population cohorts. We sought to verify this in lifelong non-smokers, among whom confounding by active smoking can be excluded, and investigate associations with circulatory and cancer deaths. METHODS: In UK Biobank, among 149 343 white never-smokers aged 40-69 years at entry, 2401 deaths occurred over a mean of 6.5-year follow-up. In the Health Surveys for England (HSE) 1995, 1996, 2001 and Scottish Health Surveys (SHS) 1998 and 2003 combined, there were 500 deaths among 6579 white never-smokers aged 40-69 years at entry, followed for a mean of 13...
July 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/28696997/number-of-offspring-and-cardiovascular-disease-risk-in-men-and-women-the-role-of-shared-lifestyle-characteristics
#12
Maria C Magnus, Stamatina Iliodromiti, Debbie A Lawlor, Janet M Catov, Scott M Nelson, Abigail Fraser
BACKGROUND: Previous studies of the number of offspring and cardiovascular disease (CVD) report conflicting findings. We re-examined this association in both sexes to clarify the role of the cardiometabolic changes that women experience during pregnancy versus shared lifestyle characteristics. METHODS: We studied 180,626 women and 133,259 men participating in the UK Biobank cohort who were free of CVD at baseline. CVD events were obtained from hospital and death registers...
July 10, 2017: Epidemiology
https://www.readbyqxmd.com/read/28678979/association-of-body-mass-index-with-cardiometabolic-disease-in-the-uk-biobank-a-mendelian-randomization-study
#13
Donald M Lyall, Carlos Celis-Morales, Joey Ward, Stamatina Iliodromiti, Jana J Anderson, Jason M R Gill, Daniel J Smith, Uduakobong Efanga Ntuk, Daniel F Mackay, Michael V Holmes, Naveed Sattar, Jill P Pell
Importance: Higher body mass index (BMI) is a risk factor for cardiometabolic disease; however, the underlying causal associations remain unclear. Objectives: To use UK Biobank data to report causal estimates of the association between BMI and cardiometabolic disease outcomes and traits, such as pulse rate, using mendelian randomization. Design, Setting, and Participants: Cross-sectional baseline data from a population-based cohort study including 119 859 UK Biobank participants with complete phenotypic (medical and sociodemographic) and genetic data...
July 5, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28649428/the-uk-me-cfs-biobank-for-biomedical-research-on-myalgic-encephalomyelitis-chronic-fatigue-syndrome-me-cfs-and-multiple-sclerosis
#14
Eliana M Lacerda, Erinna W Bowman, Jacqueline M Cliff, Caroline C Kingdon, Elizabeth C King, Ji-Sook Lee, Taane G Clark, Hazel M Dockrell, Eleanor M Riley, Hayley Curran, Luis Nacul
The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18-60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contains blood samples, aliquoted into serum, plasma, peripheral blood mononuclear cells (PBMC), red blood cells/granulocyte pellet, whole blood, and RNA (totalling 29,863 aliquots)...
2017: Open J Bioresour
https://www.readbyqxmd.com/read/28646674/a-multimodal-spatiotemporal-cardiac-motion-atlas-from-mr-and-ultrasound-data
#15
Esther Puyol-Antón, Matthew Sinclair, Bernhard Gerber, Mihaela Silvia Amzulescu, Hélène Langet, Mathieu De Craene, Paul Aljabar, Paolo Piro, Andrew P King
Cardiac motion atlases provide a space of reference in which the motions of a cohort of subjects can be directly compared. Motion atlases can be used to learn descriptors that are linked to different pathologies and which can subsequently be used for diagnosis. To date, all such atlases have been formed and applied using data from the same modality. In this work we propose a framework to build a multimodal cardiac motion atlas from 3D magnetic resonance (MR) and 3D ultrasound (US) data. Such an atlas will benefit from the complementary motion features derived from the two modalities, and furthermore, it could be applied in clinics to detect cardiovascular disease using US data alone...
June 13, 2017: Medical Image Analysis
https://www.readbyqxmd.com/read/28644851/comorbidities-in-the-diseasome-are-more-apparent-than-real-what-bayesian-filtering-reveals-about-the-comorbidities-of-depression
#16
Peter Marx, Peter Antal, Bence Bolgar, Gyorgy Bagdy, Bill Deakin, Gabriella Juhasz
Comorbidity patterns have become a major source of information to explore shared mechanisms of pathogenesis between disorders. In hypothesis-free exploration of comorbid conditions, disease-disease networks are usually identified by pairwise methods. However, interpretation of the results is hindered by several confounders. In particular a very large number of pairwise associations can arise indirectly through other comorbidity associations and they increase exponentially with the increasing breadth of the investigated diseases...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28641372/comparison-of-sociodemographic-and-health-related-characteristics-of-uk-biobank-participants-with-the-general-population
#17
Anna Fry, Thomas J Littlejohns, Cathie Sudlow, Nicola Doherty, Ligia Adamska, Tim Sprosen, Rory Collins, Naomi E Allen
UK Biobank is a population-based cohort of 500,000 participants recruited between 2006 and 2010. Approximately 9.2 million individuals aged 40-69 years who lived within 25 miles of the 22 assessment centres in England, Wales and Scotland were invited, and 5.4% participated in the baseline assessment. The representativeness of the UK Biobank cohort was investigated by comparing demographic characteristics between non-responders and responders. Sociodemographic, physical, lifestyle and health-related characteristics of the cohort were compared with nationally representative data sources...
June 21, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28633629/prevalence-of-and-risk-factors-for-severe-cognitive-and-sleep-symptoms-in-me-cfs-and-ms
#18
Vageesh Jain, Amit Arunkumar, Caroline Kingdon, Eliana Lacerda, Luis Nacul
BACKGROUND: There are considerable phenotypic and neuroimmune overlaps between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). While the precise aetiologies of both MS and ME/CFS are unclear, evidence suggests that deterioration in cognitive function is widely prevalent in patients with either condition. Little is known about differing risk factors or exposures, which may lead to severe cognitive or sleep symptoms. This study aims to gauge the extent of cognitive and sleep symptoms in ME/CFS and MS patients participating in the UK ME/CFS Biobank and identify the characteristics of those experiencing severe symptoms...
June 20, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28626828/contribution-of-risk-factors-to-excess-mortality-in-isolated-and-lonely-individuals-an-analysis-of-data-from-the-uk-biobank-cohort-study
#19
Marko Elovainio, Christian Hakulinen, Laura Pulkki-Råback, Marianna Virtanen, Kim Josefsson, Markus Jokela, Jussi Vahtera, Mika Kivimäki
BACKGROUND: The associations of social isolation and loneliness with premature mortality are well known, but the risk factors linking them remain unclear. We sought to identify risk factors that might explain the increased mortality in socially isolated and lonely individuals. METHODS: We used prospective follow-up data from the UK Biobank cohort study to assess self-reported isolation (a three-item scale) and loneliness (two questions). The main outcomes were all-cause and cause-specific mortality...
June 2017: Lancet. Public Health
https://www.readbyqxmd.com/read/28601812/cardiovascular-and-type-2-diabetes-morbidity-and-all-cause-mortality-among-diverse-chronic-inflammatory-disorders
#20
Alex Dregan, Phil Chowienczyk, Mariam Molokhia
OBJECTIVES: The present study aimed to assess the relationship between inflammatory disorders with cardiometabolic diseases and mortality within a community-based population. METHODS: The UK Biobank data were used to conduct two investigations: a cross-sectional study to estimate cardiometabolic risk and a prospective cohort study to estimate mortality risk. Binary regression analyses were used to model the association between coronary heart disease, stroke, type 2 diabetes, venous thromboembolism and peripheral artery disease diagnoses with seven inflammatory disorders (eg, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, ankylosing spondylitis (AS), systemic vasculitis, Crohn's disease and ulcerative colitis (UC))...
June 10, 2017: Heart: Official Journal of the British Cardiac Society
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