Genetic susceptibility to cardiovascular disease and risk of dementia.
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ABSTRACT:
SUBMITTER: Karlsson IK
PROVIDER: S-EPMC5534941 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
Genetic susceptibility to cardiovascular disease and risk of dementia.
Karlsson I K IK Ploner A A Song C C Gatz M M Pedersen N L NL Hägg S S
Translational psychiatry 20170530 5
Several studies have shown cardiovascular disease (CVD) to be associated with dementia, but it is not clear whether CVD per se increases the risk of dementia or whether the association is due to shared risk factors. We tested how a genetic risk score (GRS) for coronary artery disease (CAD) affects dementia risk after CVD in 13 231 Swedish twins. We also utilized summarized genome-wide association data to study genetic overlap between CAD and Alzheimer´s disease (AD), and additionally between sha ...[more]
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Project description:BackgroundPlant-based dietary patterns may be related to better cardiovascular profiles. Whether a healthy plant-based dietary index is predictive of future cardiovascular disease (CVD) across people with different genetic susceptibility remains uncertain.ObjectiveWe investigated associations of adherence to healthy plant-based diets with the incidence of CVD considering the genetic susceptibility.MethodsThis prospective cohort study included a total of 156,148 adults initially free of CVD and cancer. We calculated a healthful plant-based diet index (healthful-PDI) in which healthy plant foods received positive scores, and less healthy plant foods and animal foods received reverse scores. Genetic risk scores (GRSs) for myocardial infarction (MI) and stroke were calculated to assess interactions between healthful-PDI and GRSs.ResultsDuring 5 y of follow-up, we observed 1812 incident cases of CVD. Higher healthful-PDI was associated with a lower CVD risk [HR per 10-unit increment: 0.87 (95% CI: 0.81, 0.93) after adjusting for demographic, lifestyle, and other dietary factors (model 1); HR 0.90 (0.84, 0.97) after further adjusting for obesity and metabolic factors (model 2)]. The risk of CVD was gradually decreased in association with higher adherence to healthful-PDI, regardless of genetic susceptibility. The inverse associations of healthful-PDI with CVD were consistently observed in people with low GRS-MI [HR 0.85 (95% CI: 0.76, 0.94) in model 1; HR 0.88 (0.79, 0.97) in model 2] and those with high GRS-MI [HR 0.91 (0.82, 0.99) in model 1; HR 0.94 (0.86, 1.04) in model 2], without significant interactions (Pinteraction = 0.59 in model 1; Pinteraction = 0.66 in model 2). Similarly, higher healthful-PDI was related to a lower risk of CVD, regardless of low/high GRS-stroke.ConclusionAdherence to healthy plant-based diets may be associated with a decreased incidence of CVD in the entire population, suggesting that plant-based dietary patterns may modify the risk of CVD, regardless of genetic susceptibility.
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Project description:Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. In the PubMed database, literature was searched using keywords associated with diabetes mellitus, hypertension, dyslipidemia, white matter hyperintensities, cerebral microbleeds, and covert infarctions. Gene lists were extracted from these publications to identify shared genes and pathways for each group. This included high penetrance genes and single nucleotide polymorphisms (SNPs) identified through genome wide association studies. Most risk SNPs to both diabetes and dementia participate in the phospholipase C enzyme system and the downstream nositol 1,4,5-trisphosphate and diacylglycerol activities. Interestingly, AP-2 (TFAP2) transcription factor family and metabolism of vitamins and cofactors were associated with genetic variants that were shared by white matter hyperintensities and dementia, and by microbleeds and dementia. Variants shared by covert infarctions and dementia were related to VEGF ligand-receptor interactions and anti-inflammatory cytokine pathways. Our review sheds light on future investigations into the causative relationships behind CVDs and dementia, and can be a paradigm of the identification of dementia treatments.
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