Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.813617
Title: Adult height and the risk of cardiovascular diseases : investigating causality using genetic associations in two ethnically diverse populations
Author: Linden, Andrew Brent
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2019
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Abstract:
Background: Taller adult height has been associated with lower risk of most vascular and respiratory diseases, but higher risk of other diseases (cancer and some vascular diseases) in studies predominantly from European populations. The causal relevance of height for different cardiovascular diseases remains unclear. Methods: Instrumental variables for height were constructed from up to 3200 genetic variants having genome-wide significant association with height in published European ancestry based sources. Conventional observational and causal genetic associations (Mendelian randomisation analyses) of 1 SD (~6.5 cm) taller height with cardiovascular diseases and risk factors were assessed in 1M participants from the UK Biobank (UKB) and the China Kadoorie Biobank (CKB) studies, supplemented with data from CARDIoGRAMplusC4D and METASTROKE consortia. Results: The genetic instruments selected explained 16.9% of the variance of height in UKB but only 10.5% in CKB. The association of genetically elevated height was inversely associated with coronary artery disease (odds ratio [OR] per 1 SD taller height: 0.87; 95% CI: 0.84, 0.89; n=78 960 cases), systolic blood pressure and LDL cholesterol, positively with atrial fibrillation (1.32; 95% CI: 1.27, 1.38; n=13 365) and lean body mass, but null with ischaemic stroke overall. However, for ischaemic strokes subtypes available in METASTROKE, the association was inverse with large-vessel stroke (OR: 0.91; 95% CI: 0.84, 0.99; n=2167) and positive with cardioembolic stroke (1.13; 95% CI: 1.05, 1.22; n=2365). Genetically elevated height was also positively associated with all ischaemic stroke among UKB and CKB participants with atrial fibrillation. Observational and genetic associations with diseases were directionally consistent, and were inverse with haemorrhagic stroke (n=7819, mostly from CKB). Conclusions: Genetically elevated height is inversely associated with occlusive cardiovascular diseases, potentially mediated by blood lipids and blood pressure, but also positively associated with atrial fibrillation and cardioembolic stroke, potentially through its association with lean body mass.
Supervisor: Parish, Sarah ; Clarke, Robert Sponsor: Clarendon Fund
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.813617  DOI: Not available
Keywords: Population health ; Genetic epidemiology
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