期刊
NEUROLOGY
卷 86, 期 2, 页码 146-153出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000002263
关键词
-
资金
- Wellcome Trust
- Stroke Association [TSA 2013/01]
- Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH])
- Intramural Research Program of National Institute of Ageing (Ischemic Stroke Genetics Study [ISGS])
- National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study)
- National Institute of Neurological Disorders and Stroke (ISGS)
- National Institute of Neurological Disorders and Stroke (MGH)
- American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH)
- Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH)
- National Health and Medical Research Council (Australian Stroke Genetics Collaborative)
- Italian Ministry of Health (Milan)
- NIHR
- NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre
- FWO Flanders
- MRC
- National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London
- BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London
- Grants-in-Aid for Scientific Research [15H04772] Funding Source: KAKEN
- Medical Research Council [MR/K026992/1, G0500247, G0900295] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10168, NF-SI-0512-10019] Funding Source: researchfish
- Stroke Association [TSA2009/08, TSA2013/01, TSA2010/01] Funding Source: researchfish
- MRC [G0900295, G0500247] Funding Source: UKRI
Objective:For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms.Methods:We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations.Results:There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 x 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 x 10(-8); rs941898 [EVL], p = 4.0 x 10(-8); rs962888 [C1QL1], p = 1.1 x 10(-8); rs9515201 [COL4A2], p = 6.9 x 10(-9)).Conclusions:Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据