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

Abstract The effective sample size (ESS) is a metric used to summarize in a single term the amount of correlation in a sample. It is of particular interest when predicting the statistical power of genome-wide association studies (GWAS) based on linear mixed models. Here, we introduce an analytical form of the ESS for mixed-model GWAS of quantitative traits and relate it to empirical estimators recently proposed. Using our framework, we derived approximations of the ESS for analyses of related and unrelated samples and for both marginal genetic and gene-environment interaction tests. We conducted simulations to validate our approximations and to provide a quantitative perspective on the statistical power of various scenarios, including power loss due to family relatedness and power gains due to conditioning on the polygenic signal. Our analyses also demonstrate that the power of gene-environment interaction GWAS in related individuals strongly depends on the family structure and exposure distribution. Finally, we performed a series of mixed-model GWAS on data from the UK Biobank and confirmed the simulation results. We notably found that the expected power drop due to family relatedness in the UK Biobank is negligible.

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Socioeconomic deprivation index is associated with psychiatric disorders: an observational and genome-wide gene-environment interaction analysis in the UK Biobank cohort

Biological Psychiatry ◽

10.1016/j.biopsych.2020.11.019 ◽

2020 ◽

Author(s):

Jing Ye ◽

Yan Wen ◽

Xifang Sun ◽

Xiaomeng Chu ◽

Ping Li ◽

...

Keyword(s):

Psychiatric Disorders ◽

Interaction Analysis ◽

Socioeconomic Deprivation ◽

Deprivation Index ◽

Environment Interaction ◽

Uk Biobank ◽

Gene Environment Interaction ◽

Gene Environment ◽

Genome Wide ◽

The Uk

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Polygenic Hyperlipidemia Increases Coronary Artery Disease Risk In The Uk Biobank

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.06.266 ◽

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

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

10.1101/2020.01.29.20019620 ◽

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.

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

Scientific Reports ◽

10.1038/s41598-019-52482-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 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.

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

Circulation ◽

10.1161/circ.142.suppl_3.16105 ◽

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.

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