Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease

Grace, Christopher; Clarke, Robert; Goel, Anuj; Farrall, Martin; Watkins, Hugh; Hopewell, Jemma C.

doi:10.1038/s41598-018-25460-2

Cited by 14 publications

(22 citation statements)

References 42 publications

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“…Moreover, similar to our findings, others have shown minimal to no genetic overlap between CAD and T2D and AD [53]. Using MR, some have explored the causal relationship between CAD and AD risk [56] and found a lack of causal relevance of CAD for risk of late-onset AD after exclusion of APOE . Also, although CAD and AD show minimal genetic overlap, a genetic risk score for CAD has been shown to modify the association between CVD and AD [53].…”

Section: Discussionsupporting

confidence: 88%

Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease

et al. 2018

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Cardiovascular (CV)- and lifestyle-associated risk factors (RFs) are increasingly recognized as important for Alzheimer’s disease (AD) pathogenesis. Beyond the ε4 allele of apolipoprotein E (APOE), comparatively little is known about whether CV-associated genes also increase risk for AD. Using large genome-wide association studies and validated tools to quantify genetic overlap, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with AD and one or more CV-associated RFs, namely body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD), waist hip ratio (WHR), total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL). In fold enrichment plots, we observed robust genetic enrichment in AD as a function of plasma lipids (TG, TC, LDL, and HDL); we found minimal AD genetic enrichment conditional on BMI, T2D, CAD, and WHR. Beyond APOE, at conjunction FDR < 0.05 we identified 90 SNPs on 19 different chromosomes that were jointly associated with AD and CV-associated outcomes. In meta-analyses across three independent cohorts, we found four novel loci within MBLAC1 (chromosome 7, meta-p = 1.44 × 10−9), MINK1 (chromosome 17, meta-p = 1.98 × 10−7) and two chromosome 11 SNPs within the MTCH2/SPI1 region (closest gene = DDB2, meta-p = 7.01 × 10−7 and closest gene = MYBPC3, meta-p = 5.62 × 10−8). In a large ‘AD-by-proxy’ cohort from the UK Biobank, we replicated three of the four novel AD/CV pleiotropic SNPs, namely variants within MINK1, MBLAC1, and DDB2. Expression of MBLAC1, SPI1, MINK1 and DDB2 was differentially altered within postmortem AD brains. Beyond APOE, we show that the polygenic component of AD is enriched for lipid-associated RFs. We pinpoint a subset of cardiovascular-associated genes that strongly increase the risk for AD. Our collective findings support a disease model in which cardiovascular biology is integral to the development of clinical AD in a subset of individuals.

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Section: Discussionsupporting

confidence: 88%

Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease

et al. 2018

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“…According to genetic data from 60 801 cases of CAD and 17 008 cases of LOAD, each increment in polygenic risk score for CAD was associated with 7% higher odds of LOAD (95% CI, 1%–15%). 101 This association was no longer present after removal of the APOE locus from the polygenic risk score.…”

Section: Risk Predictionmentioning

confidence: 98%

Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association

Tsao¹,

Aday²,

Almarzooq³

et al. 2022

Circulation

3,787

2,336

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Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy. Results: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. Conclusions: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

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“…According to genetic data from 60 801 cases of CAD and 17 008 cases of LOAD, each increment in PRS for CAD was associated with 7% higher odds of LOAD (95% CI, 1%–15%). 126 This association was no longer present after removal of the APOE locus from the PRS.…”

Section: Brain Healthmentioning

confidence: 97%

Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association

Tsao¹,

Aday²,

Almarzooq³

et al. 2023

Circulation

3,530

702

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BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year’s worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year’s edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

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Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease

Cited by 14 publications

References 42 publications

Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease

Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease

Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association

Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association

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