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Ling Jun Li, Jiemin Liao, Carol Yim-lui Cheung, E SHyong Tai, Tien Y Wong, Ching-Yu Cheng; Blood Pressure and Retinal Arteriolar Narrowing: Assessing Causality through Mendelian Randomization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4506.
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Whether blood pressure (BP) is causally associated with retinal arteriolar narrowing is not clear. We aimed to generate estimates of the association between BP and retinal arteriolar narrowing that were free from confounding and reverse causation by using mendelian randomization.
A total of 6,969 participants, recruited from multi-ethnic cohorts (Chinese, Malays and Indians) in Singapore were included in this study. Quantitative retinal vascular caliber was assessed by a semi-automated computer program (Singapore I Vessel Assessment [SIVA], version 3.0). Genotyping was done using Illumina 610-quad chips. Association between BP and retinal vascular caliber was examined using both conventional linear regression and mendelian randomization framework with a genetic score of BP as an instrumental variable. The genetic score was calculated from 10 recently-discovered BP loci by weighting each SNP base on its strength of association with systolic (SBP), diastolic (DBP), or mean arterial BP (MAP).
Higher genetic risk scores were significantly associated with elevated BP (P<0.001), yet not with potential confounders (e.g. body mass index, total cholesterol, smoking, etc.). In multiple linear regression models, each 10 mm Hg increase in SBP, DBP and MAP was associated with a 1.43 μm, 2.99 μm and 2.57 μm decrease in retinal arteriolar caliber (all p<0.001), respectively. In the Mendelian randomization analysis using the genetic risk score as in instrumental variable, the estimated causal effect was a decrease in retinal arteriolar caliber of 2.28 μm (p=0.044), 4.35 μm (p=0.040) and 3.40 μm (p=0.030) for each 10 mm Hg increase in SBP, DBP and MABP, respectively.
Our data suggest that estimates on associations between BP and retinal arteriolar caliber are similar to those obtained from conventional regression analysis. Based on this mendelian randomization study, we conclude that there is a causal relationship between elevated BP and retinal arteriolar narrowing.
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