title: Assessing the Causality between Blood Pressure and Retinal Vascular Caliber through Mendelian Randomisation.
abstract: We aimed to determine the association between blood pressure (BP) and retinal vascular caliber changes that were free from confounders and reverse causation by using Mendelian randomisation. A total of 6528 participants from a multi-ethnic cohort (Chinese, Malays, and Indians) in Singapore were included in this study. Retinal arteriolar and venular caliber was measured by a semi-automated computer program. Genotyping was done using Illumina 610-quad chips. Meta-analysis of association between BP, and retinal arteriolar and venular caliber across three ethnic groups was performed both in conventional linear regression and Mendelian randomisation framework with a genetic risk score of BP as an instrumental variable. In multiple linear regression models, each 10 mm Hg increase in systolic BP, diastolic BP, and mean arterial BP (MAP) was associated with significant decreases in retinal arteriolar caliber of a 1.4, 3.0, and 2.6 μm, and significant decreases in retinal venular caliber of a 0.6, 0.7, and 0.9 μm, respectively. In a Mendelian randomisation model, only associations between DBP and MAP and retinal arteriolar narrowing remained yet its significance was greatly reduced. Our data showed weak evidence of a causal relationship between elevated BP and retinal arteriolar narrowing.
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Duke-NUS Graduate Medical School, Singapore.
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Li
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Department of Medicine, National University of Singapore and National University Health System, Singapore.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Liao
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Duke-NUS Graduate Medical School, Singapore.|Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Carol Yim-Lui
authors.initials: CY
authors.lastname: Cheung
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Duke-NUS Graduate Medical School, Singapore.
authors.forename: M Kamran
authors.initials: MK
authors.lastname: Ikram
authors.affiliation: Department of Medicine, National University of Singapore and National University Health System, Singapore.
authors.forename: Tai E
authors.initials: TE
authors.lastname: Shyong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Duke-NUS Graduate Medical School, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|Duke-NUS Graduate Medical School, Singapore.|Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000368:Aged; D015415:Biomarkers; D001794:Blood Pressure; D005006:Ethnicity; D005128:Eye Diseases / Q000453:epidemiology / Q000209:etiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D012171:Retinal Vessels / Q000473:pathology*; D012306:Risk; D012846:Singapore / Q000453:epidemiology / Q000208:ethnology
chemical_list: D015415:Biomarkers