scholarly journals A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1263
Author(s):  
Simon Vogel ◽  
Irina Rudaka ◽  
Dmitrijs Rots ◽  
Jekaterīna Isakova ◽  
Oskars Kalējs ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Score ◽  
Direct Current ◽  
Rhythm Control ◽  
Polygenic Risk Score ◽  
Single Nucleotide Variants ◽  
Polygenic Risk ◽  
Direct Current Cardioversion ◽  
Increased Risk ◽  
Af Recurrence

Background and Objectives: Recurrence of atrial fibrillation (AF) within six months after sinus rhythm restoration with direct current cardioversion (DCC) is a significant treatment challenge. Currently, the factors influencing outcome are mostly unknown. Studies have found a link between genetics and the risk of AF and efficacy of rhythm control. The aim of this study was to examine the association between eight single-nucleotide variants (SNVs) and the risk of AF development and recurrence after DCC. Materials and Methods: Regarding the occurrence of AF, 259 AF cases and 108 controls were studied. Genotypes for the eight SNVs located in the genes CAV1, MYH7, SOX5, KCNN3, ZFHX3, KCNJ5 and PITX2 were determined using high-resolution melting analysis and confirmed with Sanger sequencing. Six months after DCC, a telephone interview was conducted to determine whether AF had recurred. A polygenic risk score (PRS) was calculated as the unweighted sum of risk alleles. Multivariate regression analyses were performed to assess SNV and PRS association with AF occurrence and recurrence after DCC. Results: The risk allele of rs2200733 (PITX2) was significantly associated with the development of AF (p = 0.012, OR = 2.31, 95% CI = 1.206–4.423). AF recurred in 60% of patients and the allele generally associated with a decreased risk of AF of rs11047543 (SOX5) was associated with a greater risk of AF recurrence (p = 0.014, OR = 0.223, 95% CI = 0.067–0.738). A PRS of greater than 7 was significantly associated (p = 0.008) with a higher likelihood of developing AF after DCC (OR = 4.174, 95% CI = 1.454–11.980). Conclusions: A higher PRS is associated with increased odds of AF recurrence after treatment with DCC. PITX2 (rs2200733) is significantly associated with an increased risk of AF. The protective allele of rs11047543 (SOX5) is associated with a greater risk of AF recurrence. Further studies are needed to predict the success of rhythm control and guide patient selection towards the most efficacious treatment.

scholarly journals Associations Between Alcohol Intake and Genetic Predisposition With Atrial Fibrillation Risk in a National Biobank

2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Jennifer L. Halford ◽  
Lu-Chen Weng ◽  
Seung Hoan Choi ◽  
Sean J. Jurgens ◽  
Valerie N. Morrill ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alcohol Consumption ◽  
Risk Score ◽  
Alcohol Intake ◽  
Hazard Ratio ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Acceptable Range ◽  
Increased Risk

Background: Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We assessed the association between alcohol intake, polygenic predisposition to AF, and incident AF in the UK Biobank, a prospective cohort study. Methods: In 376 776 UK Biobank participants enrolled between 2006 and 2010, we tested alcohol consumption (stratified by the Centers of Disease Control and Prevention acceptable range of ≤98 g/wk for women or ≤196 g/wk for men; and as a continuous variable) and an AF polygenic risk score for association with incident AF. Results: Among participants (47.5% male, mean age 56.9 years), 6293 developed AF during a median of 6.9 years of follow-up. Alcohol consumption was associated with AF (hazard ratio, 1.10 [95% CI, 1.05–1.16] for intake above an acceptable range; hazard ratio, 1.04 per 100 g/wk [95% CI, 1.02–1.06]). An AF polygenic risk score was associated with AF (hazard ratio, 1.38 per SD [95% CI, 1.35–1.41]). In models including both alcohol and the AF polygenic risk score, each remained associated with AF. The 5-year cumulative risk of AF for individuals with alcohol intake above an acceptable range and in the highest decile of polygenic risk was 2.33% (95% CI, 2.07–2.59), compared with 0.69% (95% CI, 0.58–0.80) for those with alcohol intake within an acceptable range and in the lowest decile of polygenic risk. Conclusions: Alcohol consumption is associated with increased risk of AF across a range of polygenic predisposition to AF and adds to inherited and clinical predisposition to increase AF susceptibility. Preventive efforts focused on minimizing alcohol intake may be broadly applicable.

scholarly journals Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study

2017 ◽  
Vol 48 (9) ◽  
pp. 1532-1539 ◽  
Author(s):  
E. Neilson ◽  
C. Bois ◽  
T.-K. Clarke ◽  
L. Hall ◽  
E. C. Johnstone ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Familial Risk ◽  
Positive Association ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Score Analysis ◽  
Increased Risk ◽  
Heritable Disorder ◽  
Diagnostic Symptoms

AbstractBackgroundSchizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.MethodsThe current study included participants at high familial risk of schizophrenia who remained well (n= 31), who developed sub-diagnostic symptoms (n= 28) and who developed schizophrenia (n= 9) as well as healthy controls (HC) (n= 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.ResultsWe found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.ConclusionsThese results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

scholarly journals Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia

2020 ◽  
Author(s):  
Antoine Rimbert ◽  
Xavier Vanhoye ◽  
Dramane Coulibaly ◽  
Marie Marrec ◽  
Matthieu Pichelin ◽  
...  
Keyword(s):  
Liver Injury ◽  
Risk Score ◽  
Clinical Care ◽  
Liver Steatosis ◽  
Genetic Diagnosis ◽  
Density Lipoprotein ◽  
Polygenic Risk Score ◽  
Nonalcoholic Fatty Liver ◽  
Polygenic Risk ◽  
Increased Risk

Objective: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the APOB and PCSK9 genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis. Here, we compared hepatic alterations between monogenic, polygenic, and primary hypobetalipoproteinemia of unknown cause. Approach and Results: Targeted next-generation sequencing was performed in a cohort of 111 patients with hypobetalipoproteinemia to assess monogenic and polygenic origins using an LDL-C-dedicated polygenic risk score. Forty patients (36%) had monogenic hypobetalipoproteinemia, 38 (34%) had polygenic hypobetalipoproteinemia, and 33 subjects (30%) had hypobetalipoproteinemia from an unknown cause. Patients with monogenic hypobetalipoproteinemia had lower LDL-C and apolipoprotein B plasma levels compared with those with polygenic hypobetalipoproteinemia. Liver function was assessed by hepatic ultrasonography and liver enzymes levels. Fifty-nine percent of patients with primary hypobetalipoproteinemia presented with liver steatosis, whereas 21% had increased alanine aminotransferase suggestive of liver injury. Monogenic hypobetalipoproteinemia was also associated with an increased prevalence of liver steatosis (81% versus 29%, P <0.001) and liver injury (47% versus 0%) compared with polygenic hypobetalipoproteinemia. Conclusions: This study highlights the importance of genetic diagnosis in the clinical care of primary hypobetalipoproteinemia patients. It shows for the first time that a polygenic origin of hypobetalipoproteinemia is associated with a lower risk of liver steatosis and liver injury versus monogenic hypobetalipoproteinemia. Thus, polygenic risk score is a useful tool to establish a more personalized follow-up of primary hypobetalipoproteinemia patients.

P.0580 A polygenic risk score predicts an increased risk of depression in mentally healthy young adults

2021 ◽  
Vol 53 ◽  
pp. S425-S426
Author(s):  
A. Kazantseva ◽  
Y. Davydova ◽  
R. Enikeeva ◽  
R. Mustafin ◽  
M. Lobaskova ◽  
...  
Keyword(s):  
Young Adults ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Increased Risk

Atrial fibrillation in pregnancy

ESC CardioMed ◽  
2018 ◽  
pp. 2240-2244
Author(s):  
Mark Panna ◽  
Michael Kaufmann ◽  
Jamie Conti
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Weight ◽  
Direct Current ◽  
Low Molecular Weight Heparin ◽  
Fetal Monitoring ◽  
Structural Heart Disease ◽  
First Trimester ◽  
Rhythm Control ◽  
Direct Current Cardioversion ◽  
In Pregnancy

Atrial fibrillation (AF) rarely occurs during pregnancy, and when present usually occurs in the setting of congenital and/or structural heart disease such as mitral stenosis. Haemodynamically unstable patients should undergo emergent direct current cardioversion. In stable patients, rate control should be achieved with a beta blocker and/or digoxin. Rhythm control is considered whenever the risk of ongoing AF is considered high for either the mother or fetus, or in highly symptomatic AF as it restores normal haemodynamics. Direct current cardioversion is relatively safe in pregnancy, although fetal monitoring and facilities capable of performing emergent caesarean section are recommended. Anticoagulation should be considered in pregnant patients with AF at risk for stroke. Warfarin should be avoided during the first trimester due to the risk of embryopathy, and during the last 2–4 weeks of pregnancy due to bleeding risks. Low-molecular-weight heparin (preferentially) or unfractionated heparin may be used during these times. Warfarin or heparin-based products may be considered during other parts of pregnancy after fully discussing the risk and benefits of each specific anticoagulant with patients. Pregnant patients with AF should be treated as high-risk pregnancies.

scholarly journals Prostate cancer risk prediction using a polygenic risk score

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Csilla Sipeky ◽  
Kirsi M. Talala ◽  
Teuvo L. J. Tammela ◽  
Kimmo Taari ◽  
Anssi Auvinen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
Prostate Cancer Risk ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Randomised Study ◽  
Additional Information ◽  
Increased Risk ◽  
Hereditary Factors

Abstract Hereditary factors have a strong influence on prostate cancer (PC) risk and poorer outcomes, thus stratification by genetic factors addresses a critical need for targeted PC screening and risk-adapted follow-up. In this Finnish population-based retrospective study 2283 clinically diagnosed and 455 screen-detected patients from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), 2400 healthy individuals have been involved. Individual genetic risk through establishment of a polygenic risk score based on 55 PC risk SNPs identified through the Finnish subset of the Collaborative Oncological Gene-Environment Study was assessed. Men with PC had significantly higher median polygenic risk score compared to the controls (6.59 vs. 3.83, P < 0.0001). The polygenic risk score above the control median was a significant predictor of PC (OR 2.13, 95% CI 1.90–2.39). The polygenic risk score predicted the risk of PC with an AUC of 0.618 (95% CI 0.60–0.63). Men in the highest polygenic risk score quartile were 2.8—fold (95% CI 2.4–3.30) more likely to develop PC compared with men in the lowest quartile. In the FinRSPC cohort, a significantly higher percentage of men had a PSA level of ≥ 4 ng/mL in polygenic risk score quartile four compared to quartile one (18.7% vs 8.3%, P < 0.00001). Adding the PRS to a PSA-only model contributed additional information in predicting PC in the FinRSPC model. Results strongly suggest that use of the polygenic risk score would facilitate the identification of men at increased risk for PC.

scholarly journals Polygenic Risk Score Prediction for Endometriosis

2021 ◽  
Vol 3 ◽  
Author(s):  
Kirstine Kloeve-Mogensen ◽  
Palle Duun Rohde ◽  
Simone Twisttmann ◽  
Marianne Nygaard ◽  
Kristina Magaard Koldby ◽  
...  
Keyword(s):  
Risk Score ◽  
Genome Wide Association Study ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Standard Deviation Increase ◽  
Polygenic Risk ◽  
Clinical Risk ◽  
Risk Variants ◽  
Increased Risk ◽  
The Uk

Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in using genetics as part of the clinical risk assessment. The aim of this work was to investigate the discriminative ability of a polygenic risk score (PRS) for endometriosis using three different cohorts: surgically confirmed cases from the Western Danish endometriosis referral Center (249 cases, 348 controls), cases identified from the Danish Twin Registry (DTR) based on ICD-10 codes from the National Patient Registry (140 cases, 316 controls), and replication analysis in the UK Biobank (2,967 cases, 256,222 controls). Patients with adenomyosis from the DTR (25 cases) and from the UK Biobank (1,883 cases) were included for comparison. The PRS was derived from 14 genetic variants identified in a published genome-wide association study with more than 17,000 cases. The PRS was associated with endometriosis in surgically confirmed cases [odds ratio (OR) = 1.59, p = 2.57× 10−7] and in cases from the DTR biobank (OR = 1.50, p = 0.0001). Combining the two Danish cohorts, each standard deviation increase in PRS was associated with endometriosis (OR = 1.57, p = 2.5× 10−11), as well as the major subtypes of endometriosis; ovarian (OR = 1.72, p = 6.7× 10−5), infiltrating (OR = 1.66, p = 2.7× 10−9), and peritoneal (OR = 1.51, p = 2.6 × 10−3). These findings were replicated in the UK Biobank with a much larger sample size (OR = 1.28, p &lt; 2.2× 10−16). The PRS was not associated with adenomyosis, suggesting that adenomyosis is not driven by the same genetic risk variants as endometriosis. Our results suggest that a PRS captures an increased risk of all types of endometriosis rather than an increased risk for endometriosis in specific locations. Although the discriminative accuracy is not yet sufficient as a stand-alone clinical utility, our data demonstrate that genetics risk variants in form of a simple PRS may add significant new discriminatory value. We suggest that an endometriosis PRS in combination with classical clinical risk factors and symptoms could be an important step in developing an urgently needed endometriosis risk stratification tool.

scholarly journals Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population

2020 ◽  
Author(s):  
Moeen Riaz ◽  
Aamira Huq ◽  
Joanne Ryan ◽  
Suzanne G Orchard ◽  
Jane Tiller ◽  
...  
Keyword(s):  
Relative Risk ◽  
Cognitive Decline ◽  
Risk Score ◽  
Cumulative Incidence ◽  
Genetic Factors ◽  
Polygenic Risk Score ◽  
Older Individuals ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Incidence Of Dementia

AbstractImportanceFew studies have measured the effect of genetic factors on dementia and cognitive decline in a population of healthy older individuals followed prospectively.ObjectiveTo examine the effect of Apolipoprotein E (APOE) genotypes and a polygenic risk score (PRS) on incident dementia and cognitive decline in a longitudinal cohort of healthy older people.Design, Setting and ParticipantsPost-hoc genetic analysis of a randomized clinical trial population - the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrollment, participants had no history of diagnosed dementia, atherothrombotic cardiovascular disease, or permanent physical disability and were without cognitive impairment.Main Outcomes and MeasuresDementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence curves for all-cause dementia and cognitive decline were calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non-APOE variants.Results12,978 participants with European ancestry were included; 54.8% were female, and average age at baseline was 75 years (range 70 to 96). During a median 4.5 years of follow-up, 324 (2.5%) participants developed dementia and 503 (3.8%) died. Cumulative incidence of dementia to age 85 years was estimated to be 7.4% in all participants, 12.6% in APOE ε4 heterozygotes, 26.6% in ε4 homozygotes, 9.6% in the high PRS tertile, and 7.3% in the low PRS tertile. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased risk of dementia and a 1.4/1.8-fold increased risk of cognitive decline, versus ε3/ε3 (P<0.001 for both). A high PRS (top tertile) was associated with a 1.4-fold increase risk of dementia, versus the low tertile (CI 1.04-1.76, P=0.02), but was not associated with cognitive decline risk (CI 0.96-1.22, P = 0.18).Conclusions and RelevanceIncidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.KEY POINTSQuestionHow do genetic factors influence the risk of dementia and cognitive decline among healthy older individuals?FindingsWe studied cumulative incidence of dementia and cognitive decline in 12,978 healthy older individuals without cardiovascular disease or cognitive impairment at enrollment, stratified by APOE genotype and a polygenic risk score (PRS). APOE ε4 and PRS increased the relative risk of dementia, but cumulative incidence was low across all genotypes. APOE genotypes were associated with cognitive decline, but PRS was not.MeaningIncidence of dementia is low among healthy older individuals; however, genetic factors still increase relative risk.

Anti-arrhythmic drugs confer increased risks of bradyarrhythmia in patients undergoing direct current cardioversion for atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.V Rasmussen ◽  
F Dalgaard ◽  
J.L Pallisgaard ◽  
G Gislason ◽  
M.H Ruwald ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Direct Current ◽  
Clinical Decision Making ◽  
Absolute Risk ◽  
Pacemaker Implantation ◽  
Concomitant Treatment ◽  
Risk Of Death ◽  
Direct Current Cardioversion ◽  
Increased Risk ◽  
Dc Cardioversion

Abstract Background Bradyarrhythmia is a known complication to direct current cardioversion (DC-cardioversion) in patients with atrial fibrillation (AF). However, whether concomitant treatment with anti-arrhythmic drugs (AADs) is associated with an increased risk of bradyarrhythmia in relation to the procedure is unknown. Purpose To investigate the short-term risk of bradyarrhythmia associated with AAD treatment in AF patients undergoing DC-cardioversion. Methods Using Danish nationwide registers, all AF patients treated with either an AAD (amiodarone, sotalol, dronedarone, flecainide, or propafenone) or rate-lowering drugs (beta-blocker, non- dihydropyridine calcium-antagonist, or digoxin) were identified at their first DC-cardioversion between 2001 and 2016. Patients were excluded if they were under 18 or above 100 years of age or had a pacemaker or implantable cardioverter defibrillator. The event of interest was a composite outcome of either a diagnosis of bradyarrhythmia (sinoatrial arrest, atrioventricular block, or unspecified bradycardia) or a procedure of pacemaker implantation. Patients were followed from the date of DC-cardioversion until event of interest, 90 days after the procedure, or at study end. Absolute risks of bradyarrhythmic events were estimated using the Aalen-Johansen estimator taking the competing risk of death into account. Hazard ratios (HR) with 95% confidence intervals (95% CI) of bradyarrhythmic events were computed using multivariable Cox models adjusted for age, sex, calendar year, as well as relevant comorbidity and concomitant medication. Results A total of 22,344 patients were included in the study with 3,224 (14%) individuals treated with an AAD. The median age was 67 years (interquartile range [IQR] 59–73) and most were males (69%). Patients treated with AADs were younger and had more ischemic heart disease, heart failure, and valvular disease. During follow-up we identified 601 cases of bradyarrhythmia. We found an absolute risk of bradyarrhythmic events at 90 days after cardioversion of 3.7% (95% CI 3.1–4.4) for patients treated with an AAD and 2.5% (95% CI 2.3–2.7) for patients treated with rate-lowering drugs (P&lt;0.001) (Figure 1). AAD treatment conferred increased rates of bradyarrhythmia with a multivariable adjusted HR of 1.35 (95% CI: 1.10–1.65) compared to patients treated with rate-lowering drugs. Conclusion Using a large nationwide study population of patients with AF undergoing DC-cardioversion, concomitant treatment with AADs was associated with an increased risk of bradyarrhythmic events. Moreover, the absolute risks of bradyarrhythmic events after DC-cardioversion were higher than what has previously been reported. These data provide valuable insights aiding physicians in clinical decision making as well as informing patients prior to the procedure. Figure 1. Absolute risk and adjusted hazard ratio (HR) of bradyarrythmia. AAD: Anti-arrhythmic drugs. CI: Confidence Interval. Funding Acknowledgement Type of funding source: None

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