Replication of Top Loci From COL4A1/2 Associated With White Matter Hyperintensity Burden in Patients With Ischemic Stroke

Overview

Journal Stroke

Specialties Cardiology & Vascular Diseases
Neurology

Date 2020 Nov 5

PMID 33148145

Citations 5

Authors

Jiang Li

Vida Abedi

Ramin Zand

Christoph J Griessenauer

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: The purpose of this study was to replicate the top loci associated with white matter hyperintensity (WMH) phenotypes identified by large genome-wide association studies and the loci identified from the previous candidate gene studies.

Methods: A total of 946 Geisinger MyCode patients with acute ischemic stroke with validated European ancestry and magnetic resonance imaging data were included in this study. Log-transformed WMH volume, as a quantitative trait, was calculated by a fully automated quantification process. The genome-wide association studies was carried out by a linear mixed regression model (GEMMA). A candidate-single nucleotide polymorphism analysis by including known single nucleotide polymorphisms, reported from a meta-analysis and several large GWAS for WMH, was conducted in all cases and binary converted extreme cases.

Results: No genome-wide significantly associated variants were identified. In a candidate-single nucleotide polymorphism study, rs9515201 () and rs3744028 (), 2 known genetic loci, showed nominal or trend of association with the WMH volume (β=0.13 and =0.001 for rs9515201; β=0.094 and =0.094 for rs3744028), and replicated in a subset of extreme cases versus controls (odds ratio=1.78, =7.74×10 for rs9515201; odds ratio=1.53, =0.047 for rs3744028, respectively). MTHFR677 cytosine/thymine (rs1801133) also showed an association with the binary WMH with odds ratio=1.47 for T allele (=0.019).

Conclusions: Replication of COL4A1/2 associated with WMH reassures that the genetic risk factors for monogenic and polygenic ischemic stroke are shared at gene level.

Citing Articles

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Li J, Abedi V, Zand R J Clin Med. 2022; 11(20).

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