A Mendelian randomization-based exploration of red blood cell distribution width and mean corpuscular volume with risk of hemorrhagic strokes

Jundong Liu; Elizabeth L Chou; Kui Kai Lau; Peter Yat Ming Woo; Tsz Kin Wan; Ruixuan Huang; Kei Hang Katie Chan

doi:10.1016/j.xhgg.2022.100135

A Mendelian randomization-based exploration of red blood cell distribution width and mean corpuscular volume with risk of hemorrhagic strokes

HGG Adv. 2022 Aug 10;3(4):100135. doi: 10.1016/j.xhgg.2022.100135. eCollection 2022 Oct 13.

Authors

Jundong Liu¹, Elizabeth L Chou², Kui Kai Lau^{3

4}, Peter Yat Ming Woo⁵, Tsz Kin Wan⁶, Ruixuan Huang⁶, Kei Hang Katie Chan^{1

6

7}

Affiliations

¹ Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.
² Massachusetts General Hospital, Boston, MA, USA.
³ Division of Neurology, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁴ The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China.
⁵ Department of Neurosurgery, Kwong Wah Hospital, Hong Kong SAR, China.
⁶ Department of Electrical Engineering, City University of Hong Kong, Hong Kong SAR, China.
⁷ Department of Epidemiology, Centre for Global Cardiometabolic Health, Brown University, RI, USA.

Abstract

Red blood cell distribution width (RCDW) and mean corpuscular volume (MCV) are associated with different risk factors for hemorrhagic stroke. However, whether RCDW and MCV are causally related to hemorrhagic stroke remains poorly understood. Therefore, we explored the causality between RCDW/MCV and nontraumatic hemorrhagic strokes using Mendelian randomization (MR) methods. We extracted exposure and outcome summary statistics from the UK Biobank and FinnGen. We evaluated the causality of RCDW/MCV on four outcomes (subarachnoid hemorrhage [SAH], intracerebral hemorrhage [ICH], nontraumatic intracranial hemorrhage [nITH], and a combination of SAH, cerebral aneurysm, and aneurysm operations) using univariable MR (UMR) and multivariable MR (MVMR). We further performed colocalization and mediation analyses. UMR and MVMR revealed that higher genetically predicted MCV is protective of ICH (UMR: odds ratio [OR] = 0.89 [0.8-0.99], p = 0.036; MVMR: OR = 0.87 [0.78-0.98], p = 0.021) and nITH (UMR: OR = 0.89 [0.82-0.97], p = 0.005; MVMR: OR = 0.88 [0.8-0.96], p = 0.004). There were no strong causal associations between RCDW/MCV and any other outcome. Colocalization analysis revealed a shared causal variant between MCV and ICH; it was not reported to be associated with ICH. Proportion mediated via diastolic blood pressure was 3.1% (0.1%,14.3%) in ICH and 3.4% (0.2%,15.8%) in nITH. The study constitutes the first MR analysis on whether genetically elevated RCDW and MCV affect the risk of hemorrhagic strokes. UMR, MVMR, and mediation analysis revealed that MCV is a protective factor for ICH and nITH, which may inform new insights into the treatments for hemorrhagic strokes.

Keywords: Mendelian randomization; causal inference; hemorrhagic stroke; mean corpuscular volume; red blood cell distribution width.

Abstract

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