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ABSTRACT: Objective
We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke.Methods
Single-nucleotide polymorphisms associated with low- and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A-I and B (apoA-I and apoB) at the level of genomewide significance (p -8 ) in the UK Biobank were used as instrumental variables. Summary-level data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium with 514,791 individuals (60,341 ischemic stroke cases, and 454,450 non-cases).Results
Increased levels of apoB, LDL cholesterol, and triglycerides were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke in the main and sensitivity univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (p InterpretationThe present MR study reveals that apoB is the predominant trait that accounts for the etiological basis of apoB, LDL cholesterol, and triglycerides in relation to ischemic stroke, in particular large artery and small vessel stroke. Whether HDL cholesterol exerts a protective effect on ischemic stroke independent of apoA-I needs further investigation. ANN NEUROL 2020;88:1229-1236.
SUBMITTER: Yuan S
PROVIDER: S-EPMC7756401 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Annals of neurology 20201010 6
<h4>Objective</h4>We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke.<h4>Methods</h4>Single-nucleotide polymorphisms associated with low- and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A-I and B (apoA-I and apoB) at the level of genomewide significance (p < 5 × 10<sup>-8</sup> ) in the UK Biobank were used as instrumental variables. Summary-level data for ischemic str ...[more]