scholarly journals Atrial fibrillation and left atrial size and function: a Mendelian randomization study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yordi J. van de Vegte ◽  
Joylene E. Siland ◽  
Michiel Rienstra ◽  
Pim van der Harst
Keyword(s):  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Stroke Volume ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Maximal Volume ◽  
Pitx2 Gene ◽  
The Uk ◽  
Leave One Out ◽  
And Function

AbstractAtrial fibrillation (AF) patients have enlarged left atria (LA), but prior studies suggested enlarged atria as both cause and consequence of AF. The aim of this study is to investigate the causal association between AF and LA size and function. In the UK Biobank, all individuals with contoured cardiovascular magnetic resonance data were selected. LA maximal volume (LA max), LA minimal volume (LA min), LA stroke volume and LA ejection fraction were measured and indexed to body surface area (BSA). Two-sample Mendelian randomization analyses were performed using 84 of the known genetic variants associated with AF to assess the association with all LA size and function in individuals without prevalent AF. A total of 4274 individuals (mean age 62.0 ± 7.5 years, 53.2% women) were included. Mendelian randomization analyses estimated a causal effect between genetically determined AF and BSA-indexed LA max, LA min, and LA ejection fraction, but not between AF and LA stroke volume. Leave-one-out analyses showed that the causal associations were attenuated after exclusion of rs67249485, located near PITX2 gene. Our results suggest that AF causally increases LA size and decreases LA ejection fraction. The AF risk allele of rs67249485, located near the PITX2 gene, contributes strongly to these associations.

scholarly journals Causal effect of atrial fibrillation/flutter on chronic kidney disease: A bidirectional two-sample Mendelian randomization study

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261020
Author(s):  
Masahiro Yoshikawa ◽  
Kensuke Asaba ◽  
Tomohiro Nakayama
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Association Studies ◽  
European Population ◽  
Genome Wide Association Studies ◽  
The Uk

Chronic kidney disease (CKD) and atrial fibrillation are both major burdens on the health care system worldwide. Several observational studies have reported clinical associations between CKD and atrial fibrillation; however, causal relationships between these conditions remain to be elucidated due to possible bias by confounders and reverse causations. Here, we conducted bidirectional two-sample Mendelian randomization analyses using publicly available summary statistics of genome-wide association studies (the CKDGen consortium and the UK Biobank) to investigate causal associations between CKD and atrial fibrillation/flutter in the European population. Our study suggested a causal effect of the risk of atrial fibrillation/flutter on the decrease in serum creatinine-based estimated glomerular filtration rate (eGFR) and revealed a causal effect of the risk of atrial fibrillation/flutter on the risk of CKD (odds ratio, 9.39 per doubling odds ratio of atrial fibrillation/flutter; 95% coefficient interval, 2.39–37.0; P = 0.001), while the causal effect of the decrease in eGFR on the risk of atrial fibrillation/flutter was unlikely. However, careful interpretation and further studies are warranted, as the underlying mechanisms remain unknown. Further, our sample size was relatively small and selection bias was possible.

scholarly journals Low-density lipoprotein cholesterol and atrial fibrillation; A Mendelian randomization study using UK-Biobank data

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Michail Katsoulis ◽  
Spiros Denaxas ◽  
Riyaz Patel ◽  
Harry Hemingway
Keyword(s):  
Atrial Fibrillation ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hospital Episode Statistics ◽  
Uk Biobank ◽  
Low Density Lipoprotein Cholesterol ◽  
Hospital Episode ◽  
The Uk

ABSTRACTObjectivesWe used data from UK-Biobank that were linked with Hospital Episode Statistics and Office for National Statistics to assess the relationship between low-density lipoprotein cholesterol (LDL-C) and atrial fibrillation (AF). In this study, we applied Mendelian randomization in order to find out whether there is a causal effect of LDL-C to AF. ApproachWe used data from the UK Biobank (~500,000 subjects) which is linked with electronic health records. At baseline (2006-2010), participants from across the UK took part in this project. They have undergone measures, provided blood, urine and saliva samples for future analysis, detailed information about themselves and agreed to have their health followed. Information in relation to the development of atrial fibrillation was derived from a) the enrollment of the participants (self-reported events), b) their hospitalization before and after their recruitment to UK-Biobank (confirmed events from Hospital Episode Statistics) and c) the death certificates [confirmed events from Office for National Statistics]. We also used genetic data from the analyses of the participants’ blood sample that have been stored. We used Mendelian randomization to capture the effect of LDL-C to AF. As instruments, we used a genetic predisposition risk score (GPRs) for LDL-C, which was created as a weighted sum of the 18 most significant SNPs related to LDL-C, as there were documented in Global Lipid Consortium, in 18 out of 22 chromosomes. We ran a logistic regression model, using AF as outcome and GPRs as exposure. ResultsOur final sample consisted of 144,092 individuals, for which we have valid information for their genetic data. The AF cases in this sample were 3207, most of which were identified from Hospital Episode Statistics (hospitalization of the participants). From the Mendelian randomization study, from our preliminary results, we found a weak positive relationship between GPRs and AF, when we did not adjust for any covariate [OR per one unit increase of GPRs=1.08, 95% CI= (0.95-1.22)] and results remained practically the same when we adjusted for age and sex [OR=1.09, 95% CI= (0.96-1.24 )]. ConclusionWe observed a weak positive association between LDL-C and AF in this study. This is the first Mendelian randomization approach that focuses on this relationship. More Mendelian randomization studies should be performed in order to identify the causal effect of LDL-C to AF. The use of electronic health records will facilitate the conduction of similar studies.

Causal Association Between Atopic Dermatitis and Inflammatory Bowel Disease: A 2-Sample Bidirectional Mendelian Randomization Study

2021 ◽  
Author(s):  
Christa Meisinger ◽  
Dennis Freuer
Keyword(s):  
Inflammatory Bowel Disease ◽  
Atopic Dermatitis ◽  
Bowel Disease ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
The Other ◽  
Uk Biobank ◽  
Inflammatory Bowel ◽  
The Uk

Abstract Background Observational studies postulated an association between atopic dermatitis (AD) and inflammatory bowel disease (IBD). However, it remains unclear whether this relationship is causal. Methods To determine whether AD is causally related to IBD and vice versa, a 2-sample Mendelian randomization study was conducted. Independent genetic instruments from the largest available genome-wide association study for AD (EAGLE eczema consortium without the 23andMe study including 10,788 cases and 30,047 controls) were used to investigate the association with IBD in the UK Biobank study (7045 cases, 456,327 controls) and a second European IBD sample (12,882 cases, 21,770 controls). Results Atopic dermatitis was strongly associated with higher risk of IBD as a whole (odds ratio [OR], 1.107; 95% confidence interval [CI], 1.035; 1.183; P = .003) in the UK Biobank study. The positive association was not significant in the other IBD study (OR, 1.114; 95% CI, 0.956; 1.298), but in meta-analyses of results from the 2 studies, the strong association could be confirmed (OR, 1.11; 95% CI, 1.04; 1.18). When evaluating the causal relationship in the other direction, IBD as a whole did not show an association with AD. Subtype analyses revealed that AD was suggestively associated with ulcerative colitis (UC; OR, 1.149; 95% CI, 1.018; 1.297) but not Crohn’s disease (CD). However, there was a suggestive association between CD and AD (OR, 1.034; 95% CI, 1.004; 1.064) but not UC and AD. Conclusions This study supports a causal effect between AD and IBD—but not between IBD and AD. There seems to be considerable differences between UC and CD regarding their specific associations with AD. These findings have implications for the management of IBD and AD in clinical practice.

scholarly journals Causal effect of atrial fibrillation on brain white or grey matter volume: A Mendelian randomization study

2020 ◽  
Author(s):  
Sehoon Park ◽  
Soojin Lee ◽  
Yaerim Kim ◽  
Semin Cho ◽  
Kwangsoo Kim ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
White Matter ◽  
Grey Matter ◽  
Mendelian Randomization ◽  
Brain Volume ◽  
Causal Effect ◽  
Grey Matter Volume ◽  
Volume Loss ◽  
White Matter Volume ◽  
Matter Volume

AbstractBackgroundAtrial fibrillation (AF) and brain volume loss are prevalent in older individuals. Further study investigating the causal effect of AF on brain volume is warranted.MethodsThis study was a Mendelian randomization (MR) analysis. The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis and included 537,409 individuals of European ancestry. The outcome summary statistics for quantile-normalized white or grey matter volume measured by magnetic resonance imaging were provided by the previous GWAS of 8426 white British UK Biobank participants. The main MR method was the inverse variance weighted method, supported by sensitivity MR analysis including MR-Egger regression and the weighted median method. The causal estimates from AF to white or grey matter volume were further adjusted for effects of any stroke or ischemic stroke by multivariable MR analysis.ResultsA higher genetic predisposition for AF (one standard deviation increase) was significantly associated with lower white matter volume [beta −0.128 (−0.208, −0.048)] but not grey matter volume [beta −0.041 (−0.101, 0.018)], supported by all utilized sensitivity MR analyses. The multivariable MR analysis indicated that AF is causally linked to lower white matter volume independent of the stroke effect.ConclusionsAF is a causative factor for white matter volume loss. The effect of AF on grey matter volume was inapparent in this study. A future trial is necessary to confirm whether appropriate AF management can be helpful in preventing cerebral white matter volume loss or related brain disorders in AF patients.

scholarly journals Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study

2021 ◽  
Vol 7 ◽  
Author(s):  
Shucheng Si ◽  
Jiqing Li ◽  
Yunxia Li ◽  
Wenchao Li ◽  
Xiaolu Chen ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Causal Effect ◽  
Heart Diseases ◽  
Cerebrovascular Diseases ◽  
European Ancestry ◽  
Uk Biobank ◽  
Tyg Index ◽  
Metabolic Outcomes ◽  
Meta Regression ◽  
The Uk

Background: The causal evidence of the triglyceride–glucose (TyG) index, as well as the joint exposure of higher glucose and triglyceride on the risk of cardio-cerebrovascular diseases (CVD), was lacking.Methods: A comprehensive factorial Mendelian randomization (MR) was performed in the UK Biobank cohort involving 273,368 individuals with European ancestry to assess and quantify these effects. The factorial MR, MR-PRESSO, MR-Egger, meta-regression, sensitivity analysis, positive control, and external verification were utilized. Outcomes include major outcomes [overall CVD, ischemic heart diseases (IHD), and cerebrovascular diseases (CED)] and minor outcomes [angina pectoris (AP), acute myocardial infarction (AMI), chronic IHD (CIHD), heart failure (HF), hemorrhagic stroke (HS), and ischemic stroke (IS)].Results: The TyG index significantly increased the risk of overall CVD [OR (95% CI): 1.20 (1.14–1.25)], IHD [OR (95% CI): 1.22 (1.15–1.29)], CED [OR (95% CI): 1.14 (1.05–1.23)], AP [OR (95% CI): 1.29 (1.20–1.39)], AMI [OR (95% CI): 1.27 (1.16–1.39)], CIHD [OR (95% CI): 1.21 (1.13–1.29)], and IS [OR (95% CI): 1.22 (1.06–1.40)]. Joint exposure to genetically higher GLU and TG was significantly associated with a higher risk of overall CVD [OR (95% CI): 1.17 (1.12–1.23)] and IHD [OR (95% CI): 1.22 (1.16–1.29)], but not with CED. The effect of GLU and TG was independent of each other genetically and presented dose–response effects in bivariate meta-regression analysis.Conclusions: Lifelong genetic exposure to higher GLU and TG was jointly associated with higher cardiac metabolic risk while the TyG index additionally associated with several cerebrovascular diseases. The TyG index could serve as a more sensitive pre-diagnostic indicator for CVD while the joint GLU and TG could offer a quantitative risk for cardiac metabolic outcomes.

scholarly journals Identification of Atrial Fibrillation Risk Variant RS2200733 In Indian Young Adult Population

2021 ◽  
Author(s):  
Aarthi Manoharan ◽  
Ravikumar Sambandam ◽  
Vithiavathi Sathish ◽  
Vishnu Bhat
Keyword(s):  
Atrial Fibrillation ◽  
Indian Population ◽  
Adult Population ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Risk Variant ◽  
Pitx2 Gene ◽  
Young Adult Population ◽  
Cardiac Structure And Function ◽  
And Function

Abstract Atrial fibrillation (AF) is a common cardiac arrhythmia that affects millions of people. a substantial genetic contribution to AF has been identified by number of studies over the years. The SNP that is often linked with genetic predisposition to AF is rs2200733 located in the intergenic region close to PITX2 gene which is implicated in cardiac structure and function. rs2200733 is commonly observed in major global populations. Our study aimed to establish the prevalence of this important SNP among young healthy adults in order to assess the risk of genetic susceptibility which could culminate into AF later in life. The study identified a substantial frequency of rs2200733 in Indian population at 21%.

scholarly journals Causal Effect of Obstructive Sleep Apnea on Atrial Fibrillation: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Weiqi Chen ◽  
Xueli Cai ◽  
Hongyi Yan ◽  
Yuesong Pan
Keyword(s):  
Atrial Fibrillation ◽  
Obstructive Sleep Apnea ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Genome Wide Association ◽  
Sensitivity Analyses ◽  
Genome Wide ◽  
Inverse Variance ◽  
Obstructive Sleep ◽  
Increased Risk

Background Obstructive sleep apnea (OSA) has shown to be associated with an increased risk of atrial fibrillation in observational studies. Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causal effect of OSA on atrial fibrillation. Methods and Results We used a 2‐sample Mendelian randomization (MR) method to evaluate the causal effect of OSA on atrial fibrillation. Summary data on genetic variant‐OSA association were obtained from a recently published genome‐wide association studies with up to 217 955 individuals and data on variant‐atrial fibrillation association from another genome‐wide association study with up to 1 030 836 individuals. Effect estimates were evaluated using inverse‐variance weighted method. Other MR analyses, including penalized inverse‐variance weighted, penalized robust inverse‐variance weighted, MR‐Egger, simple median, weighted median, weighted mode‐based estimate and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods were performed in sensitivity analyses. The MR analyses in both the fixed‐effect and random‐effect inverse‐variance weighted models showed that genetically predicted OSA was associated with an increased risk of atrial fibrillation (odds ratio [OR], 1.21; 95% CI, 1.12–1.31, P <0.001; OR, 1.21; 95% CI, 1.11–1.32, P <0.001) using 5 single nucleotide polymorphisms as the instruments. MR‐Egger indicated no evidence of genetic pleiotropy (intercept, −0.014; 95% CI, −0.033 to 0.005, P =0.14). Results were robust using other MR methods in sensitivity analyses. Conclusions This MR analysis found that genetically predicted OSA had causal effect on an increased risk of atrial fibrillation.

scholarly journals 144 Atrial and ventricular phenotypes in a cohort of patients with functional tricuspid regurgitation: clinical, echocardiographic, and prognostic aspects

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Mara Gavazzoni ◽  
Francesca Heilbron ◽  
Denisa Florescu ◽  
Pellegrino Ciampi ◽  
Andrada C Guta ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Right Ventricle ◽  
Tricuspid Regurgitation ◽  
Composite Endpoint ◽  
Right Atrial ◽  
P Value ◽  
Functional Tricuspid Regurgitation ◽  
And Function ◽  
Rv Function

Abstract Aims Atrial functional tricuspid regurgitation (A-FTR) has emerged as a newly recognized phenotype of functional tricuspid regurgitation (FTR), occurring in patients with atrial fibrillation and right atrial (RA) dilation but normal right ventricular (RV) size and function. Its prevalence, echocardiographic features, and prognosis have not yet clarified since most evidence to date has included indiscriminately FTR patients with A-FTR and ventricular form (V-FTR). Aim of this study was to investigate the differences between these two phenotypes of FTR in terms of clinical correlates, echocardiographic aspects, and prognosis. Methods and results A total of 180 consecutive patients with moderate to severe FTR referred for echocardiography in two Italian centres were retrospectively enrolled. A-FTR was defined as: (1) longstanding atrial fibrillation; (2) PASP &lt;50 mmHg; (3) left ventricular ejection fraction &gt; 60% (complete according to the ACC guidelines); and (4) no significant left side valve disease. 3D TTE was used for the quantitative assessment of TR and chamber sizing and function. The composite endpoint of death for any cause and heart failure (HF) hospitalization was used as primary outcome of this analysis; secondary endpoint was HF-hospitalization. Patients with A-FTR were 30% of the population; they were older than those one with V-FTR; with higher systolic blood pressure and less advanced symptoms. Chronic obstructive pulmonary disease was more prevalent in V-FTR. Patients with V-FTR had larger 3D-derived right ventricle (RV) volumes, both diastolic and systolic, while right ventricle ejection fraction (RVEF) was similar. RV functional parameters as TAPSE, RVFWLS, and RVGLS were significantly lower in the V-FTR patients as well as all the parameters of RV-pulmonary arterial (PA) coupling. After a median follow-up of 24 months (IQR: 2–48), 72 patients (40%) reached the primary endpoint and 64 (36%) hospitalized for HF. The rate of composite endpoint tended to be lower in A-FTR than in V-FTR (29% vs. 44%, P-value: 0.1); the rate of hospitalization for HF was higher in V-FTR patients (22% vs. 41%, P-value: 0.04). Correlates of combined endpoint in both groups were: functional class of dyspnoea (NYHA class III–IV vs. I–II), severe TR grade (HR in V-FTR: 2.88 [1.63–5.06], P &lt; 0.01; HR in A-FTR: 8[3–17], P &lt; 0.01); RV volumes, RA volumes. Estimated SPAP as well as all the parameters of RV function and of RV-PA coupling were correlates of prognosis only in V-FTR; conversely, parameters of TA dimensions were related to combined Endpoint in A-FTR phenotype, while RV function and RV-PA coupling indexes did not. Conclusions Patients having A-FTR have an incidence of combined endpoint slightly different, without reaching a statistically significant difference, thus remarking the fact that A-FTR could not be considered ‘more benign’ and should therefore be targeted. Prognostic predictors are different between A-.FTR and V-FTR patients.

scholarly journals The effect of BMI and type 2 diabetes on socioeconomic status: a two-sample multivariable Mendelian randomization study

2021 ◽  
Author(s):  
Sara Pedron ◽  
Christoph F Kurz ◽  
Lars Schwettmann ◽  
Michael Laxy
Keyword(s):  
Type 2 Diabetes ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Univariate Analysis ◽  
Causal Link ◽  
Marginal Effect ◽  
Nucleotide Polymorphisms ◽  
Socioeconomic Outcomes ◽  
The Uk

OBJECTIVE <p>To assess the independent causal effect of BMI and type 2 diabetes (T2D) on socioeconomic outcomes applying two-sample Mendelian randomization (MR) analysis.</p> <p>RESEARCH DESIGN AND METHODS</p> <p>We carried out univariate and multivariate two-sample MR to jointly assess the effect BMI and T2D on socioeconomic outcomes. We used overlapping genome-wide significant single nucleotide polymorphisms (SNPs) for BMI and T2D as instrumental variables. Their causal impact on household income and regional deprivation was assessed using summary-level data from the UK Biobank. </p> <p>RESULTS</p> <p>In the univariate analysis, higher BMI was related with lower income (marginal effect of 1-SD increase in BMI [β=-0.092 (95% CI: -0.138; -0.047)] and higher deprivation [β=0.051 (95% CI: 0.022; 0.079)]. In the multivariate MR, the effect of BMI controlling for diabetes was slightly lower for income and deprivation. Diabetes was not associated with these outcomes.</p> <p>CONCLUSIONS</p> <p>High BMI, but not diabetes, shows a causal link with socioeconomic outcomes. </p>

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