scholarly journals Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1663
Author(s):  
David B. Emmert ◽  
Vladimir Vukovic ◽  
Nikola Dordevic ◽  
Christian X. Weichenberger ◽  
Chiara Losi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
General Population ◽  
Large Scale ◽  
Familial Aggregation ◽  
Population Sample ◽  
P Value ◽  
Supraventricular Arrhythmia ◽  
Risk Alleles ◽  
A Genome ◽  
Metabolic Screening

Atrial fibrillation (AF) is a supraventricular arrhythmia deriving from uncoordinated electrical activation with considerable associated morbidity and mortality. To expand the limited understanding of AF biological mechanisms, we performed two screenings, investigating the genetic and metabolic determinants of AF in the Cooperative Health Research in South Tyrol study. We found 110 AF cases out of 10,509 general population individuals. A genome-wide association scan (GWAS) identified two novel loci (p-value < 5 × 10−8) around SNPs rs745582874, next to gene PBX1, and rs768476991, within gene PCCA, with genotype calling confirmed by Sanger sequencing. Risk alleles at both SNPs were enriched in a family detected through familial aggregation analysis of the phenotype, and both rare alleles co-segregated with AF. The metabolic screening of 175 metabolites, in a subset of individuals, revealed a 41% lower concentration of lysophosphatidylcholine lysoPC a C20:3 in AF cases compared to controls (p-adj = 0.005). The genetic findings, combined with previous evidence, indicate that the two identified GWAS loci may be considered novel genetic rare determinants for AF. Considering additionally the association of lysoPC a C20:3 with AF by metabolic screening, our results demonstrate the valuable contribution of the combined genomic and metabolomic approach in studying AF in large-scale population studies.

scholarly journals Mental health and caregiving experiences of family carers supporting people with psychosis

2021 ◽  
Vol 30 ◽  
Author(s):  
J. Sin ◽  
J. Elkes ◽  
R. Batchelor ◽  
C. Henderson ◽  
S. Gillard ◽  
...  
Keyword(s):  
Mental Health ◽  
Risk Factors ◽  
General Population ◽  
Large Scale ◽  
Controlled Trial ◽  
Population Sample ◽  
Poor Mental Health ◽  
Mental Wellbeing ◽  
Family Carers ◽  
Negative Experience

Abstract Aims Family carers supporting an individual with psychosis often experience poorer mental health, however, little is known about specific risk factors among these carers. We investigated the associations between demographic, caregiving characteristics and mental health outcomes in family carers supporting an individual with psychosis and compared carers' outcomes with general population norms. Methods We analysed baseline data from the COPe-support randomised controlled trial of online psychoeducation and peer support for adult carers supporting an individual with psychosis between 2018 and 2020. We collected carers' demographic and health outcome data, including wellbeing using Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS as primary outcome), quality of life using EQ-5D-5L and caregiving experience assessed with Experience of Caregiving Inventory. We tested associations between carers' demographic and caregiving characteristics for each outcome in turn and meta-analysed carers' WEMWBS and EQ-5D-5L with Health Survey England (HSE) general population data from 2016 and 2017, respectively. Results The 407 carers of people with psychosis had a mean WEMWBS score of 42.2 (s.d. 9.21) and their overall weighted pooled WEMWBS score was 7.3 (95% confidence interval (CI) −8.6 to −6.0, p < 0.01) lower than the HSE general population sample, indicating carers have poorer mental wellbeing by more than double the minimum clinically important difference of 3 points on WEMWBS. Among all caring relationships, partners had poorer wellbeing compared to parents with lower WEMWBS score (−6.8, −16.9 to 3.3, p = 0.03). Single carers had significantly poorer wellbeing (−3.6, −5.6 to −1.5, p < 0.01) and a more negative caregiving experience than those who were cohabiting. Spending more than 35 h per week caregiving increased carers' negative experience significantly (p = 0.01). Conclusion Carers of people with psychosis have poorer mental health than non-carers. Partners, lone carers and those spending more than 35 h per week on caring were found to be most at risk of poor mental health. Based on the results, we advocate that the details of carers for individuals with psychosis should be added to the existing carers or severe mental illness registers at all general practitioner surgeries and for their wellbeing screened routinely. Future large-scale prospective studies are needed to develop a predictive model to determine risk factors, hence to aid early identification of carers' support needs. Such understandings are also useful to inform tailored intervention development.

scholarly journals Validation of the Rasch-based Depression Screening in a large scale German general population sample

2010 ◽  
Vol 8 (1) ◽  
pp. 105 ◽  
Author(s):  
Thomas Forkmann ◽  
Maren Boecker ◽  
Markus Wirtz ◽  
Heide Glaesmer ◽  
Elmar Brähler ◽  
...  
Keyword(s):  
General Population ◽  
Large Scale ◽  
Population Sample ◽  
Depression Screening ◽  
General Population Sample

scholarly journals KNOWLEDGE, ATTITUDES, AND PRACTICES TOWARD CORONAVIRUS DISEASE-19 INFECTION AMONG RESIDENTS OF DELHI NCR, INDIA: A CROSS-SECTIONAL SURVEY BASED STUDY

2020 ◽  
pp. 110-116
Author(s):  
UBADA AQEEL ◽  
MOHAMMAD DAUD ALI ◽  
ZEENAT IQBAL ◽  
MOHD. AAMIR MIRZA
Keyword(s):  
General Population ◽  
Large Scale ◽  
Online Survey ◽  
Social Stigma ◽  
Insurance Coverage ◽  
Personal Hygiene ◽  
P Value ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Attitudes And Practices

Objective: In the given study, we have carried out a survey among general population of Delhi NCR (India) for the knowledge, perceptions, and attitude toward coronavirus disease (COVID-19) and also attempted to reach to a few conclusions in the form of recommendations. Methods: A cross-sectional questionnaire based online survey (using Google Forms) was conducted between April 2020 and May 2020 to investigative knowledge, perceptions, and attitude toward COVID-19. Chi-square test was used for the computation of p-value. Results: There were total 823 respondents, with 43.01% females and 56.98% males. Around 73.74% respondents believe that it has become a social stigma. About 75.09% were of the opinion that sneezing etiquettes can help in curbing the infection. About 93.43% of study population follows the personal hygiene, 24.78% wished to get insurance coverage. Similarly, interesting data were collected over different aspects of COVID-19. Conclusions: The current pandemic is the first exposure at such a large scale to the existing population but with the progression of time, authorities and general population are collating knowledge about the same. It is to be fought at all the fronts such as medical, social, economic, and psychological. Hence, this type of survey becomes an important tool in decision making.

scholarly journals Causal Association Between Birth Weight and Atrial Fibrillation: Evidence from a Two-Sample Mendelian Randomization Analysis

2020 ◽  
Author(s):  
Songzan Chen ◽  
Fangkun Yan ◽  
Tian Xu ◽  
Yao Wang ◽  
Kaijie Zhang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Birth Weight ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
P Value ◽  
Causal Association ◽  
Genome Wide ◽  
A Genome ◽  
Mr Study

Abstract Background Although several observational studies have shown an association between birth weight (BW) and atrial fibrillation (AF), controversy remains. In this study, we aimed to explore the role of elevated BW on the etiology of AF. Methods A two-sample Mendelian randomization (MR) study was designed to infer the causality. The genetic data on the associations of single nucleotide polymorphisms (SNPs) with BW and AF were separately obtained from two large-scale genome-wide association study with up to 321,223 and 1,030,836 individuals respectively. SNPs were identified at a genome-wide significant level (p-value < 5 × 10− 8). The inverse variance-weighted (IVW) with fixed effects method was performed to obtain causal estimates as our primary analysis. MR-Egger regression was conducted to assess the pleiotropy and sensitivity analyses with various statistical methods were applied to evaluate the robustness of the results. Results In total, 122 SNPs were identified as the genetic instrumental variables. MR analysis revealed a causal effect of elevated BW on AF (OR = 1.21, 95% CI = 1.13–1.29, p-value = 2.39 × 10− 8). The MR-Egger regression suggested no evidence of directional pleiotropy (intercept = 0.00, p-value = 0.62). All the results in sensitivity analyses were consistent with the primary result, which confirmed the causal association between BW and AF. Conclusions The findings from the two-sample MR study indicate a causal effect of elevated BW on AF. This suggests a convenient and effective method to ease the burden of AF by reducing the number of newborns with elevated BW.

Risk factors for silent and symptomatic atrial fibrillation in an elderly population screening programme:a report from the noninvasive monitoring for early detection of atrial fibrillation (NOMED-AF)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mitrega ◽  
B Sredniawa ◽  
J Stokwiszewski ◽  
A Sokal ◽  
J Boidol ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
General Population ◽  
Population Sample ◽  
Population Based ◽  
Public Institution ◽  
Elderly Subjects ◽  
Funding Source ◽  
Cross Sectional ◽  
Independent Risk Factors

Abstract Background It is important to determine the risk factors that predispose elderly subjects from the general population for symptomatic atrial fibrillation and atrial flutter (AF/AFl), but population-based data for silent AF (SAF) are limited. Aim To study risk factors for symptomatic AF and SAF in a general population screen for subjects age ≥65 where continuous monitoring was performed up to 30 days with a vest-based monitor. Methods The NOMED-AF study was a cross-sectional study based on a representative population sample (n=3014; mean age 77.5±7.9 years; F=1479). In 680 subjects AF/AFl (including 279 with SAF) was diagnosed. Independent risk factors for AF/AFl and SAF were determine on weighted data using multiple logistic regression. Results The independent risk factors for AF/AFl and SAF are summarised in the Table. There are nine independent risk factors for AF/AFl and eight for SAF. Revascularization and obesity were independently associated with patients with (symptomatic) AF/AFl, and CKD was associated with SAF. Other risk factors are common for AF/AFl and SAF. Conclusions AF/AFl and SAF have slightly different associated clinical risk factors in this representative population sample aged ≥65 years. This may facilitated targeted screening programmes for high risk subgroups, particularly for SAF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The research has received funding from the National Centre for Research and Development under grant agreement (STRATEGMED2/269343/18/NCBR/2016)

Abstract 4403: Significant Single Nucleotide Polymorphism Associated with Atrial Fibrillation Located on Chromosome 4q25 in a Whole Genome Association Study and Association with Left Atrial Gene Expression

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mina K Chung ◽  
David R Van Wagoner ◽  
Jonathan D Smith ◽  
Robert C Wirka ◽  
Eric J Topol ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Association Study ◽  
Left Atrial ◽  
Additive Model ◽  
P Value ◽  
Q Value ◽  
Tissue Samples ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

Introduction: Heritability studies of atrial fibrillation (AF) suggest a complex genetic basis for common AF. Recently a locus on chromosome 4q25 was associated with AF in a genome-wide association study (GWAS), but the mechanism by which this locus is associated with AF is unknown. Methods: To identify genetic variations associated with AF, we performed an analysis of AF as a secondary phenotype from a case-control GWAS of myocardial infarction. 210,178 autosomal SNPs of high quality were genotyped in 138 AF cases and 546 controls. Stratified score tests of the trend/additive model and general genotypic model were performed for each SNP. Genomic control and multidimensional scaling were used to control and assess population stratification. The SNP meeting genome-wide significance was genotyped in 46 left atrial appendage tissue samples for which we obtained expression levels for 22,184 transcripts. Cis expression traits within 1 megabase of the top SNP were tested for association with the SNP genotypes. Results: One SNP (rs4611994) met our per-SNP genome-wide significance thresholds (both a conservative Bonferroni threshold or a more liberal FDR-based threshold) for association with AF, which was in perfect linkage disequilibrium with the locus on chromosome 4q25 found in the deCODE genetics AF study (r 2 with SNP rs2200733=1.0). This SNP yielded an AF odds ratio of 2.28 under the additive model, with a p-value using genomic control/general genotype model of 5.0E-08, and a minor allele frequency 0.13 in controls and 0.25 in AF cases, and a genome-wide p-value of 0.046 by permutation analysis. In the 46 left atrial tissue samples, cis analysis demonstrated significant association between rs4611994 genotype and expression of LRIT3 (Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3) with q-value 2.22E-03 and the C isoform of PITX2 with q-value 7.50E-03. Conclusions: Our GWAS for common AF has replicated the AF-associated locus on chromosome 4q25. The genotype at this locus was correlated with cis regulation of the LRIT3 and PITX2C transcripts, suggesting these genes as candidates for mechanistic studies.

scholarly journals Predicting silent atrial fibrillation in the elderly – NOMED-AF study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Mitrega ◽  
G Y H Lip ◽  
B Sredniawa ◽  
A Sokal ◽  
W Streb ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
General Population ◽  
Risk Stratification ◽  
Population Sample ◽  
Male Gender ◽  
Public Institution ◽  
Dash Score ◽  
Clinical Risk

Abstract Background Asymptomatic (“silent”) atrial fibrillation is common and associated with poor outcomes. It is important to determine the risk factors that predispose elderly individuals from the general population to atrial fibrillation (AF). However, population-based data for silent AF (SAF) are limited. Design First, to study the risk factors for symptomatic AF and SAF in an elderly (≥65 years) general population. Second, to develop a risk stratification model for predicting SAF. Methods Continuous ECG monitoring was performed for up to 30 days using a vest-based system in a cohort from NOMED-AF, a cross-sectional study based on a nationwide population sample. The independent risk factors for AF and SAF were determined using multiple logistic regression. ROC analysis was applied to validate developed risk stratification score. Results From the total cohort of 3014 subjects, AF was diagnosed in 680 individuals (mean age, 77.5±7.9; 50.1% men) with AF, and of these, 279 (41%) had SAF. Independent associations with an increased risk of AF were age, male gender, coronary heart disease, thyroid diseases, prior ischemic stroke or transient ischemic attack (ICS/TIA), diabetes, heart failure, chronic kidney disease (CKD), obesity (BMI&gt;30) and NT-proBNP &gt;125 ng/ml. Prior revascularization was negatively associated with risk of AF. The main risk factors for SAF were age, male gender, prior ICS/TIA, diabetes, heart failure, CKD and NT-proBNP &gt;125 ng/ml. We developed a simple clinical risk scale (MR-DASH score) which had good prediction in the derivation cohort (AUC 0.726) and the validation cohort (AUC 0.730). Conclusions SAF is associated with various clinical risk factors in a population sample of individuals ≥65 years. Stratifying individuals from the general population according to their risk for SAF may be possible using the MR-DASH score, facilitating targeted screening programs of individuals with high risk of SAF FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Centre for Research and Development

scholarly journals MULTITRAIT ANALYSIS EXPANDS GENETIC RISK FACTORS IN CARDIOEMBOLIC STROKE

2021 ◽  
Author(s):  
Jara Carcel-Marquez ◽  
Elena Muino ◽  
Cristina Gallego-Fabrega ◽  
Natalia Cullell ◽  
Miquel Lledos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Genome Wide Association Study ◽  
Cardiac Development ◽  
Cardioembolic Stroke ◽  
P Value ◽  
Genome Wide ◽  
Independent Analysis ◽  
A Genome ◽  
Electrical Impulses ◽  
Multitrait Analysis

Background and Purpose: The genetic architecture of cardioembolic stroke (CES) is still poorly understood. Atrial fibrillation (AF) is the main cause of CES, with which it shares heritability. We aimed to discover novel loci associated with CES by performing a Multitrait Analysis of the GWAS (MTAG) with atrial fibrillation genetic data. Methods: For the MTAG analysis we used the MEGASTROKE cohort, which comprises European patients with CES and controls (n=362,661) and an AF cohort composed of 1,030,836 subjects. Regional genetic pleiotropy of the significant results was explored using an alternative Bayesian approach with GWAS-pairwise method. A replication was performed in an independent European cohort comprising 9,105 subjects using a Genome Wide Association Study (GWAS). Results: MTAG-CES analysis revealed 40 novel and significant loci (p-value<5x10-8) associated with CES, four of which had not previously been associated with AF. A significant replication was assessed for eight novel loci: CAV1, IGF1R, KIAA1755, NEURL1, PRRX1, SYNE2, TEX41 and WIPF1, showing a p-value<0.05 in the CES vs controls independent analysis. KIAA1755, a locus not previously described associated with AF. Interestingly, 51 AF risk loci were not associated with CES according to GWAS-pairwise analysis. Gene Ontology (GO) analysis revealed that these exclusive AF genes from the 51 loci participate in processes related mainly to cardiac development, whereas genes associated with AF and CES participate mainly in muscle contraction and the conduction of electrical impulses. Conclusions: We found eight new loci associated with CES. In addition, this study provides novel insights into the pathogenesis of CES, highlighting multiple candidate genes for future functional experiments.

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