scholarly journals Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank

2021 ◽  
pp. 1-10
Author(s):  
Anna E. Fürtjes ◽  
Jonathan R. I. Coleman ◽  
Jess Tyrrell ◽  
Cathryn M. Lewis ◽  
Saskia P. Hagenaars
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Correlations ◽  
Uk Biobank ◽  
Waist To Hip Ratio ◽  
Artery Disease ◽  
The Uk ◽  
Cardiometabolic Traits ◽  
Shared Genetic

Abstract Background People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits. Methods In a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits. Results Several traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations. Conclusions This large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.

scholarly journals Phenotypic Associations and Shared Genetic Etiology between Bipolar Disorder and Cardiometabolic Traits

2020 ◽  
Author(s):  
Anna E. Fürtjes ◽  
Jonathan R.I. Coleman ◽  
Jess Tyrrell ◽  
Cathryn M. Lewis ◽  
Saskia P. Hagenaars
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Bipolar Disorder ◽  
Genetic Etiology ◽  
Waist To Hip Ratio ◽  
Polygenic Risk ◽  
Artery Disease ◽  
Cardiometabolic Traits ◽  
Shared Genetic

AbstractBackgroundPeople with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. BPD has a bidirectional relationship with cardiometabolic traits, but their shared etiology is poorly understood. This study aimed to examine the phenotypic associations and shared genetic etiology between BPD and various cardiometabolic traits.MethodsIn a subset of the UK Biobank sample (N = 67,317) we investigated phenotypic associations between BPD (n = 4,155) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine the shared genetic etiology, polygenic risk scores and genetic correlations were calculated between BPD and these traits.ResultsSeveral cardiometabolic traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin (HbA 1c), low systolic blood pressure, high body mass index, high waist-to-hip ratio, as well as stroke, coronary artery disease and type 2 diabetes diagnosis. Polygenic risk score regressions showed that higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease, and type 2 diabetes was associated with increased risk for bipolar disorder. These associations were not replicated when using genetic correlations.ConclusionsThis large study identified phenotypic cardiometabolic risk factors for BPD. Moreover, it found that comorbidities between BPD and waist-to-hip ratio, triglycerides, type 2 diabetes and coronary artery disease may be based on shared genetic etiology. These results provide a better understanding of the phenotypic and genetic comorbidity between BPD and cardiometabolic traits.

Associations of observational and genetically determined caffeine intake with coronary artery disease and diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Said ◽  
Y.J Van De Vegte ◽  
N Verweij ◽  
P Van Der Harst
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Cox Regression ◽  
Caffeine Intake ◽  
Uk Biobank ◽  
Genome Wide ◽  
Artery Disease ◽  
Genetically Determined

Abstract Background Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes (T2D). However, whether these associations are causal remains unknown. Objectives This study aimed to identify genetic variants associated with caffeine intake, and to investigate possible causal links between genetically determined caffeine intake and CAD or T2D. Additionally, we aimed to replicate previous observational findings between caffeine intake and CAD or T2D. Methods Genome wide associated studies (GWAS) were performed on caffeine intake from coffee, tea or both in 407,072 UK Biobank participants. Identified variants were used in a two-sample Mendelian randomization (MR) approach to investigate evidence for causal links between caffeine intake and CAD in CARDIoGRAMplusC4D (60,801 cases; 123,504 controls) or T2D in DIAGRAM (26,676 cases; 132,532 controls). Observational associations were tested within UK Biobank using Cox regression analyses. Results Moderate observational caffeine intakes from coffee or tea were associated with lower risks of CAD or T2D compared to no or high intake, with the lowest risks at intakes of 120–180 mg/day from coffee for CAD (HR=0.77 [95% CI: 0.73–0.82; P<1e-16]), and 300–360 mg/day for T2D (HR=0.76 [95% CI: 0.67–0.86]; P=1.57e-5). GWAS identified 51 novel genetic loci associated with caffeine intake, enriched for central nervous system genes. In contrast to observational analyses, MR analyses in CARDIoGRAMplusC4D and DIAGRAM yielded no evidence for causal links between caffeine intake and the development of CAD or T2D. Conclusions MR analyses indicate caffeine intake might not protect against CAD or T2D, despite protective associations in observational analyses. Manhattan_plot_CaffeineIntake Funding Acknowledgement Type of funding source: None

scholarly journals Polygenic Hyperlipidemia Increases Coronary Artery Disease Risk In The Uk Biobank

2019 ◽  
Vol 287 ◽  
pp. e92
Author(s):  
P. Ripatti ◽  
J.T. Rämö ◽  
S. Söderlund ◽  
I. Surakka ◽  
A.S. Havulinna ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Disease Risk ◽  
Coronary Artery Disease Risk ◽  
Uk Biobank ◽  
Artery Disease ◽  
The Uk

scholarly journals Apolipoprotein E genotype, lifestyle and coronary artery disease: gene-environment interaction analyses in the UK Biobank population

2020 ◽  
Author(s):  
Maxime M Bos ◽  
Lina de Vries ◽  
Patrick CN Rensen ◽  
Ko Willems van Dijk ◽  
Gerard Jan Blauw ◽  
...  
Keyword(s):  
Physical Activity ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Fish Intake ◽  
Uk Biobank ◽  
Pufa Intake ◽  
Oily Fish ◽  
Artery Disease ◽  
The Uk ◽  
Cad Risk

AbstractBackgroundCarriers of the APOE ε4 genotype have an increased risk for developing coronary artery disease (CAD), but there is preliminary evidence that lifestyle factors interact with APOE genotype on CAD risk. Here, we assessed the interactions of physical activity, oily fish intake and polyunsaturated fatty acid (PUFA) intake with APOE genotype on risk of incident cardiovascular disease in a large population of middle-aged individuals.Methods and ResultsThe present study was embedded in the UK Biobank population and comprised 344,092 European participants (mean age: 56.5 years, 45.7% men) without a history of CAD. Information regarding physical activity, oily fish intake and PUFA intake was collected through questionnaires, and information on incident CAD through linkage with hospital admission records. Analyses were performed using Cox proportional hazard models adjusted for age and sex. From these analyses, higher physical activity level and a higher intake of oily fish were associated with a lower incidence of CAD. These associations were similar across all APOE isoform groups (p-values for interaction > 0.05). A higher PUFA intake was only associated with a lower CAD risk in APOE ε4 carriers (hazard ratio: 0.76, 95% confidence interval: 0.62,0.90), however, no statistically significant interaction was observed (p-valueinteraction = 0.137).ConclusionWhile higher physical activity, fish intake and PUFA intake all decreased the risk of CAD, no evidence for interaction of these lifestyle factors with APOE genotype was observed in UK Biobank participants. Interventions intended to reduce cardiovascular risk might therefore be similarly effective across the APOE isoform carriers.

scholarly journals Effects of blood lead on coronary artery disease and its risk factors: a Mendelian Randomization study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
C. Mary Schooling ◽  
Glen D. Johnson ◽  
Jean Grassman
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Blood Lead ◽  
Uk Biobank ◽  
1000 Genomes ◽  
A Genome ◽  
Artery Disease ◽  
The Uk

Abstract Lead is pervasive, although lead exposure has fallen in response to public health efforts. Observationally, lead is positively associated with cardiovascular disease and hypertension. We used separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization) based on 13 single nucleotide polymorphisms (SNP), from a genome wide association study, strongly (p-value < 5 × 10−6) and independently associated with blood lead. These SNPs were applied to a large extensively genotyped coronary artery disease (CAD) study (cases = <76014, controls = <264785) largely based on CARDIoGRAPMplusC4D 1000 Genomes and the UK Biobank SOFT CAD, to the UK Biobank (n = 361,194) for blood pressure and to the DIAGRAM 1000 genomes diabetes case (n = 26,676)-control (n = 132,532) study. SNP-specific Wald estimates were combined using inverse variance weighting, MR-Egger and MR-PRESSO. Genetically instrumented blood lead was not associated with CAD (odds ratio (OR) 1.01 per effect size of log transformed blood lead, 95% confidence interval (CI) 0.97, 1.05), blood pressure (systolic −0.18 mmHg, 95% CI −0.44 to 0.08 and diastolic −0.03 mmHg, 95% CI −0.09 to 0.15) or diabetes (OR 0.98, 95% CI 0.92 to 1.03) using MR-PRESSO estimates corrected for an outlier SNP (rs550057) from the highly pleiotropic gene ABO. Exogenous lead may have different effects from endogenous lead; nevertheless, this study raises questions about the role of blood lead in CAD.

Abstract 16105: Depression Modulates Polygenic Risk of Cardiovascular and Cardiometabolic Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael C Honigberg ◽  
Amy Sarma ◽  
Nandita Scott ◽  
Malissa J Wood ◽  
Pradeep Natarajan
Keyword(s):  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Health Behaviors ◽  
Genetic Risk ◽  
Cardiometabolic Disease ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Artery Disease ◽  
The Uk

Introduction: Depression is associated with an increased risk of coronary artery disease (CAD). Whether depression modifies genetic risk of cardiovascular and cardiometabolic disease is unknown. Methods: We included genotyped, unrelated European ancestry individuals in the UK Biobank. Using genome-wide significant single nucleotide polymorphisms (SNPs) from studies external to the UK Biobank, we generated polygenic risk scores (PRS) for coronary artery disease (CAD, 74 SNPs), hypertension (75 SNPs), type 2 diabetes (T2D, 64 SNPs), atrial fibrillation (25 SNPs), and ischemic stroke (11 SNPs). Participants were stratified by PRS for each condition as low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk. Cox models tested the association of depression frequency with each incident condition among individuals with high PRS, with adjustment for age, sex, the first 20 principal components, genotyping array, and Townsend deprivation index. Additional models further adjusted for health behaviors (exercise, tobacco and alcohol use, vegetable and fresh fruit intake) and tested associations across the PRS spectrum. Results: Among 348,083 individuals, 78,664 (22.6%) reported depression in the past 2 weeks, including 14,776 (4.2%) with depression more than half of days. Depression burden modified the risk of incident CAD across the spectrum of CAD polygenic risk (Figure 1A). Among individuals with high PRS, lack of depression was associated with lower risk of incident CAD (HR 0.70, 95% 0.58-0.86), hypertension (HR 0.58, 95% CI 0.50-0.67), T2D (HR 0.48, 95% CI 0.41-0.55), and atrial fibrillation (HR 0.74, 95% CI 0.62-0.89) compared to those with a high burden of depression. These risk reductions were minimally attenuated after further adjustment for health behaviors (Figure 1B). Conclusions: Lower burden of depression was associated was decreased risks of cardiovascular disease among individuals at high genetic cardiovascular risk.

scholarly journals Obesity and Diabetes Type 2-Related Complications

2017 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Diabetic Foot ◽  
Macrovascular Complications ◽  
Diabetic Patients ◽  
Waist To Hip Ratio ◽  
Obesity And Diabetes ◽  
Artery Disease ◽  
Microvascular And Macrovascular Complications

Background: Obesity and diabetes are common public health problems among Saudis. Among diabetics, weight management is more challenging, because of the weight-promoting effect of most glucose-lowering therapies. Aim of study: To investigate if central obesity is associated with development of complications among type 2 diabetic patients. Patients and Methods: During February 2015, a total of 111 (39 males and 72 females) type 2 Saudi diabetics attending the Diabetics Clinic at King Salman North West Armed Forces Hospital, Tabuk City, Saudi Arabia, were included in this study. Collected data included Patients’ demographic characteristics, blood pressure, waist and hip circumference as well as microvascular and macrovascular complications of diabetes. Obesity was defined as having waist-to-hip ratio above the acceptable range (i.e., <0.8 among females and <0.9 among females). Results: Mean age of participants (SD) was 55.4 (12.6) years. According to the waist-to-hip ratio, 89 patients (80.2%) were obese. Two thirds of patients were hypertensive (66.7%), 21.6% had retinopathy, 17.1% had nephropathy, 14.4% had polyneuropathy, 17.1% had diabetic foot, while 19.8% had coronary artery disease. Prevalence rates for all complications among type 2 diabetics were higher among obese than non-obese patients, with significant differences regarding hypertension (p=0.004), retinopathy (p=0.030) diabetic foot (p=0.017); nephropathy (p=0.015) and coronary artery disease (p=0.045). Conclusions: Prevalence of obesity is high among type 2 Saudi diabetics. Diabetes related complications are more common among obese diabetics. Weight reduction is an important step toward prevention of diabetes-related microvascular and macrovascular complications.

scholarly journals Genetic comorbidity between major depression and cardio-metabolic disease, stratified by age at onset of major depression

2019 ◽  
Author(s):  
SP Hagenaars ◽  
JRI Coleman ◽  
S Choi ◽  
H Gaspar ◽  
MJ Adams ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Body Mass Index ◽  
Coronary Artery ◽  
Major Depression ◽  
Body Mass ◽  
Genetic Correlations ◽  
Polygenic Risk ◽  
Artery Disease

AbstractIntroductionIt’s imperative to understand the specific and shared aetiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression.MethodsPolygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic aetiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in eleven data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank.ResultsAll cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression.ConclusionsThe phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic aetiology irrespective of the age depression first presents.

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