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

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 p...

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Published in:Stroke (00392499) Vol. 51; no. 12; pp. 3751 - 3756
Main Authors: Li, Jiang, Abedi, Vida, Zand, Ramin, Griessenauer, Christoph J.
Format: research Journal Article
Published: Lippincott Williams & Wilkins Dec2020
Online Access:View this record in EBSCOhost
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      jtl: Stroke (00392499)
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      dt: Dec2020
      vid: 51
      iid: 12
      pid: 433
      pub: Lippincott Williams & Wilkins
      place: Baltimore, Maryland
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        147158318
        147158318
        NLM33148145
        147158318
        10.1161/STROKEAHA.120.030260
        NLM33148145
        147158318
      ppf: 3751
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        atl: Replication of Top Loci From COL4A1/2 Associated With White Matter Hyperintensity Burden in Patients With Ischemic Stroke.
      aug:
        au:
          Li, Jiang
          Abedi, Vida
          Zand, Ramin
          Griessenauer, Christoph J.
        affil: Department of Molecular and Functional Genomics, Geisinger, Danville, PA (J.L., V.A.).
      sug:
      ab: 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 (COL4A2) and rs3744028 (TRIM65), 2 known genetic loci, showed nominal or trend of association with the WMH volume (β=0.13 and P=0.001 for rs9515201; β=0.094 and P=0.094 for rs3744028), and replicated in a subset of extreme cases versus controls (odds ratio=1.78, P=7.74×10-4 for rs9515201; odds ratio=1.53, P=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 (P=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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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