Identifying Observational and Causal Factors for Cardiovascular Diseases through Large-scale Cohorts
type: CreativeWork
description: Background Starting in the 1940s, prospective studies like the Framingham Heart Study helped scientists generate new knowledge on risk factors for cardiovascular diseases. While these data sources set in motion the decline in age-adjusted cardiovascular disease seen over the last five decades, they were limited by their size in the kinds of research questions they could answer. Since then, larger data sources have emerged, some with genotyping on the order of hundreds of thousands of people, that have afforded immense power. Here, I use multiple data sources that contain more than 500,000 individuals, some with and some without genetic data, to identify novel insights into observational and causal risk factors for cardiovascular diseases. Objectives To use observational (non-genetic) epidemiological approaches to examine and compare risk factors for subtypes of stroke. To elucidate the observational and causal associations of kidney function with stroke and coronary heart disease (CHD). To perform Mendelian randomization (MR) using transcriptomic and proteomic data on CHD. To develop race- and sex- specific risk prediction models for subtypes of heart failure. Results Observational risk factor profiles for subarachnoid hemorrhage and intracerebral hemorrhage, two subtypes of hemorrhagic stroke, differed quantitatively, suggesting distinct pathogenesis. I found U-shaped observational associations between estimated glomerular filtration rate (eGFR) and CHD. Associations between genetically-predicted eGFR and CHD displayed a threshold effect starting roughly around 75 mL/min/1.73 m2, highlighting the potential for reno-protective therapeutics, like sodium-glucose cotransporter 2 inhibitors, to prevent primary CHD events. I prioritized 582 genes/proteins within 275 genomic regions with possible causal relevance to CHD. I identified cilostazol, an inhibitor of Phosphodiesterase 3A (PDE3A), as a repurposing opportunity for the primary prevention of CHD and a safer alterna…
abstract: Background Starting in the 1940s, prospective studies like the Framingham Heart Study helped scientists generate new knowledge on risk factors for cardiovascular diseases. While these data sources set in motion the decline in age-adjusted cardiovascular disease seen over the last five decades, they were limited by their size in the kinds of research questions they could answer. Since then, larger data sources have emerged, some with genotyping on the order of hundreds of thousands of people, that have afforded immense power. Here, I use multiple data sources that contain more than 500,000 individuals, some with and some without genetic data, to identify novel insights into observational and causal risk factors for cardiovascular diseases. Objectives To use observational (non-genetic) epidemiological approaches to examine and compare risk factors for subtypes of stroke. To elucidate the observational and causal associations of kidney function with stroke and coronary heart disease (CHD). To perform Mendelian randomization (MR) using transcriptomic and proteomic data on CHD. To develop race- and sex- specific risk prediction models for subtypes of heart failure. Results Observational risk factor profiles for subarachnoid hemorrhage and intracerebral hemorrhage, two subtypes of hemorrhagic stroke, differed quantitatively, suggesting distinct pathogenesis. I found U-shaped observational associations between estimated glomerular filtration rate (eGFR) and CHD. Associations between genetically-predicted eGFR and CHD displayed a threshold effect starting roughly around 75 mL/min/1.73 m2, highlighting the potential for reno-protective therapeutics, like sodium-glucose cotransporter 2 inhibitors, to prevent primary CHD events. I prioritized 582 genes/proteins within 275 genomic regions with possible causal relevance to CHD. I identified cilostazol, an inhibitor of Phosphodiesterase 3A (PDE3A), as a repurposing opportunity for the primary prevention of CHD and a safer alterna…
author: Gaziano, Liam
language: eng
keywords: Epidemiology
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/e714595d-2a6f-431f-bc35-47322d0a5bfe/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-01-04
date modified: 2026-07-22T22:24:03Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.97102