scholarly journals Rare GATA6 variants associated with risk of congenital heart disease phenotypes in 200,000 UK Biobank exomes

2021 ◽  
Author(s):  
Simon G Williams ◽  
Dominic Byrne ◽  
Bernard Keavney
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Rare Variants ◽  
Uk Biobank ◽  
Sequencing Data ◽  
Chd Risk ◽  
Increased Risk ◽  
Sequencing Studies ◽  
The Uk

Several genes have been associated with congenital heart disease (CHD) risk in previous GWAS and sequencing studies, but studies involving larger numbers of case samples remain needed to facilitate further understanding of what remains a complex and largely uncharacterised genetic etiology. Here we use whole exome sequencing data from 200,000 samples in the UK Biobank to assess ultra-rare and potentially pathogenic variation associated with increased risk of CHD. Our findings indicate that rare variants in GATA6, presumably with a lesser effect on gene function than those causing severe CHD phenotypes, or buffered by other genetic and environmental effects during development, are also associated with minor CHD conditions, specifically bicuspid aortic valve, the most common CHD condition.

scholarly journals Two Common MTHFR Gene Polymorphisms (C677T and A1298C) and Fetal Congenital Heart Disease Risk: An Updated Meta-Analysis with Trial Sequential Analysis

2018 ◽  
Vol 45 (6) ◽  
pp. 2483-2496 ◽  
Author(s):  
Rui Zhang ◽  
Caihong Huo ◽  
Xingning Wang ◽  
Bo Dang ◽  
Yaning Mu ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Congenital Heart ◽  
Sequential Analysis ◽  
Recessive Model ◽  
Trial Sequential Analysis ◽  
Chd Risk ◽  
Increased Risk

Background/Aims: Published studies indicated that the MTHFR gene polymorphisms C677T and A1298C are associated with congenital heart disease (CHD) risk in children, but obtained inconsistent results. Our study aims to reach a more accurate association between these two polymorphisms and CHD risk. Methods: Eligible studies were obtained by screening the PubMed, Embase, China National Knowledge Infrastructure, Wan Fang and VIP databases based on designed searching strategy. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Moreover, a trial sequential analysis was introduced to confirm the positive results and an RNA secondary structure analysis was also applied to discover the potential molecular mechanism. Results: Based on thirty-two published articles, involving 6988 congenital heart disease subjects and 7579 healthy controls, the pooled results from the C677T polymorphism in the fetal population showed increased risks in allelic model (OR=1.32, 95%CI=1.14-1.53), recessive model (OR=1.69, 95%CI=1.25-2.30), dominant model (OR=1.35, 95%CI=1.11-1.64), heterozygote model (OR=1.20, 95%CI=1.01-1.41) and homozygote model (OR=1.75, 95%CI=1.31-2.33). An increased risk was only detected in the A1298C polymorphism in the overall fetal popalation in a recessive model (OR=1.42, 95%CI=1.10-1.84). In the subgroup stratified by region, sample size, genotyping method and source of controls, the increased risks were widely observed in both the C677T and A1298C polymorphisms with CHD risk. Furthermore, trial sequential analysis confirmed our positive results, and the RNA secondary structure analysis detected the changes in the RNA secondary structure caused by the mutant 677T allele and 1298C allele. Conclusion: In summary, we found that the MTHFR C677T polymorphism is associated with a significant increased risk in congenital heart disease in the fetal population. Moreover, an increased risk in the CC genotype of MTHFR A1298C polymorphism was observed, but the protective role of the 1298C allele needs further study.

scholarly journals Strategies for the management of pulmonary arterial hypertension in patients with congenital heart disease

2020 ◽  
Vol 4 (S1) ◽  
Author(s):  
Nathalie Liew ◽  
Zoya Rashid ◽  
Robert Tulloh
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Congenital Heart ◽  
Standard Management ◽  
Advanced Therapies ◽  
Pulmonary Arterial ◽  
The Uk

Abstract Background Pulmonary hypertension (PH) is commonly seen in adults who have congenital heart disease (CHD). Therapy is available for pulmonary arterial hypertension (PAH) and has greatly benefitted many patients with PAH related to CHD (PAH-CHD) over the last 15 years, with evidence of improved quality of life and prognosis in those with Eisenmenger syndrome and repaired PAH-CHD. In this review, we describe the standard management and advanced therapies for PAH, which are available in specialist PH centres around the UK and Ireland, and how these are used in PAH-CHD. Decisions around the choice of therapy are governed by commissioning and available evidence. Conclusion We explain the different pathways for action and the variety of medications now at our disposal to help this important group of patients.

scholarly journals Neighbourhood maternal socioeconomic status indicators and risk of congenital heart disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Miao ◽  
Sandra Dunn ◽  
Shi Wu Wen ◽  
Jane Lougheed ◽  
Jessica Reszel ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Household Income ◽  
Congenital Heart ◽  
Population Based ◽  
Income Poverty ◽  
Lower Odds ◽  
Logistic Regression Models ◽  
Chd Risk

Abstract Background This study aimed to examine the relationships between various maternal socioeconomic status (SES) indicators and the risk of congenital heart disease (CHD). Methods This was a population-based retrospective cohort study, including all singleton stillbirths and live births in Ontario hospitals from April 1, 2012 to March 31, 2018. Multivariable logistic regression models were performed to examine the relationships between maternal neighbourhood household income, poverty, education level, employment and unemployment status, immigration and minority status, and population density and the risk of CHD. All SES variables were estimated at a dissemination area level and categorized into quintiles. Adjustments were made for maternal age at birth, assisted reproductive technology, obesity, pre-existing maternal health conditions, substance use during pregnancy, rural or urban residence, and infant’s sex. Results Of 804,292 singletons, 9731 (1.21%) infants with CHD were identified. Compared to infants whose mothers lived in the highest income neighbourhoods, infants whose mothers lived in the lowest income neighbourhoods had higher likelihood of developing CHD (adjusted OR: 1.29, 95% CI: 1.20–1.38). Compared to infants whose mothers lived in the neighbourhoods with the highest percentage of people with a university or higher degree, infants whose mothers lived in the neighbourhoods with the lowest percentage of people with university or higher degree had higher chance of CHD (adjusted OR: 1.34, 95% CI: 1.24–1.44). Compared to infants whose mothers lived in the neighbourhoods with the highest employment rate, the odds of infants whose mothers resided in areas with the lowest employment having CHD was 18% higher (adjusted OR: 1.18, 95% CI: 1.10–1.26). Compared to infants whose mothers lived in the neighbourhoods with the lowest proportion of immigrants or minorities, infants whose mothers resided in areas with the highest proportions of immigrants or minorities had 18% lower odds (adjusted OR: 0.82, 95% CI: 0.77–0.88) and 16% lower odds (adjusted OR: 0.84, 95% CI: 0.78–0.91) of CHD, respectively. Conclusion Lower maternal neighbourhood household income, poverty, lower educational level and unemployment status had positive associations with CHD, highlighting a significant social inequity in Ontario. The findings of lower CHD risk in immigrant and minority neighbourhoods require further investigation.

OP29 The prevalence of congenital heart disease in the UK: a population-based register study

2014 ◽  
Vol 68 (Suppl 1) ◽  
pp. A17.1-A17
Author(s):  
KE Best ◽  
E Draper ◽  
J Kurinczuk ◽  
S Stoianova ◽  
D Tucker ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Population Based ◽  
Register Study ◽  
The Uk

scholarly journals LVNC – A review

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
Lisa Brandon ◽  
◽  
Brian Kerr ◽  
Ken McDonald ◽  
◽  
...  
Keyword(s):  
Heart Failure ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Gold Standard ◽  
Congenital Heart ◽  
Imaging Techniques ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
Disease Modifying ◽  
No Gold Standard

LVNC is a relatively new clinical entity, with a significant increase in awareness and diagnosis in recent years. Currently the aetiology and pathogenesis of LVNC remains uncertain, alongside prevalence, however the diagnosis of LVNC appears to be increasing with improving imaging techniques. For educational purposes involving a rare clinical condition, we present the case of a 52 year old gentleman who was diagnosed with LV non compaction via ECHO and CMR. Interestingly it was noted two of his children had congenital heart disease, one daughter had Tetralogy of Fallot, and a second daughter had both an ASD and VSD. Challenges facing LVNC involve difficulty of diagnosis with no gold standard yet available, uncertainty of benefit with standard disease modifying therapies for HF-REF, and apparent increased risk of arrhythmias suggesting early ICD placement may be warranted for patients. Keywords: Hr-Ref; heart failure; lv non compaction; arrhythmias; lcd Risk.

scholarly journals Nutritional assessment and associated factors in children with congenital heart disease in Ethiopia.

2021 ◽  
Author(s):  
Temesgen Tsega Desta
Keyword(s):  
Congenital Heart Disease ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Associated Factors ◽  
Congenital Heart ◽  
Nutritional Assessment ◽  
Failure To Thrive ◽  
Cross Sectional ◽  
Care Givers ◽  
Increased Risk

ABSTRACT Infants and children with congenital heart disease exhibit a range of delays in weight gain and growth. In some instances, the delay can be relatively mild, whereas in other cases, cause the failure to thrive. OBJECTIVES To determine the nutritional status and associated factors of pediatric patients with congenital heart disease. MATERIAL AND METHODS A cross sectional analytical study was done over a period of 6months (Feb to Jul 2020). A total of 228 subjects with congenital heart disease that come to the cardiac center during the study period where included until the calculated sample size was attained. Data was collected from patient card and care givers of the children included in the study after obtaining their informed consent using data inquiry sheet. RESULTS A total of 228 children from age 3month to 17yrs. Most of the subjects had acyanotic heart disease accounting for 87.7%. The overall prevalence of wasting, underweight and stunting were 41.3%, 49.1% and 43% respectively. Among this children with congenital heart disease those with PAH were found more likely have wasting compared to those without PAH with an odds of 1.9 (95% CI: 1.0-3.4) and also greater chance of being stunted with an odds of 1.9 (95% CI: 1.0-3.4). children above 5years of age were 2.3 times more likely to be underweight. CONCLUSION Malnutrition is a major problem of patients with CHD. Pulmonary hypertension and older age are associated with increased risk of undernutrition. KEYWORDS: Acyanotic, cyanotic, Pulmonary hypertension, underweight, wasting and stunting.

Abstract 19314: Impact of Body Mass Index on Clinical Outcomes in Complex Adult Congenital Heart Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Norihisa Toh ◽  
Ines Uribe Morales ◽  
Zakariya Albinmousa ◽  
Tariq Saifullah ◽  
Rachael Hatton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Mass Index ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Adult Congenital Heart Disease ◽  
Cardiac Events ◽  
Increased Risk ◽  
Adult Congenital

Background: Obesity can adversely affect most organ systems and increases the risk of comorbidities likely to be of consequence for patients with complex adult congenital heart disease (ACHD). Conversely, several studies have demonstrated that low body mass index (BMI) is a risk factor for heart failure and adverse outcomes after cardiac surgery. However, there are currently no data regarding the impact of BMI in ACHD. Methods: We examined the charts of 87 randomly selected, complex ACHD patients whose first visit to our institution was at 18-22 years old. Patients were categorized according to BMI at initial visit: underweight (BMI < 18.5 kg/m 2 ), normal (BMI 18.5 - 24.9 kg/m 2 ), overweight/obese (BMI ≥ 25 kg/m 2 ). Events occurring during follow-up were recorded. Data was censured on 1/1/2014. Cardiac events were defined as a composite of cardiac death, heart transplantation or admission for heart failure. Results: The cohort included patients with the following diagnoses: tetralogy of Fallot n=31, Mustard n=28, Fontan n=17, ccTGA n=9 and aortic coarctation n=2. The median (IQR) duration of follow-up was 8.7 (4.2 - 1.8) years. See table for distribution and outcomes by BMI category. Cardiac events occurred in 17/87 patients. After adjustment for age, sex, and underlying disease, the underweight group had increased risk of cardiac events (HR=12.9, 95% CI: 2.8-61.5, p < 0.05). Kaplan-Meier curves demonstrate the poorer prognosis of underweight patients (Figure). Conclusions: Underweight was associated with increased risk of late cardiac events in ACHD patients. We were unable to demonstrate significant overweight/obesity impact.

Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank

2021 ◽  
pp. bjophthalmol-2021-319508
Author(s):  
Xianwen Shang ◽  
Zhuoting Zhu ◽  
Yu Huang ◽  
Xueli Zhang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Heart Disease ◽  
Age Related Macular Degeneration ◽  
Hospital Inpatient ◽  
Uk Biobank ◽  
Age Related ◽  
Incident Dementia ◽  
Increased Risk ◽  
The Uk ◽  
Systemic Condition

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

Sign in / Sign up

Export Citation Format

Share Document