Journal article

Genetic variation in PLEKHG1 is associated with white matter hyperintensities (n=11,226)

Matthew Traylor, Daniel J Tozer, Iain D Croall, Danuta M Lisiecka Ford, Abiodun Olubunmi Olorunda, Giorgio Boncoraglio, Martin Dichgans, Robin Lemmens, Jonathan Rosand, Natalia S Rost, Peter M Rothwell, Cathie LM Sudlow, Vincent Thijs, Loes Rutten-Jacobs, Hugh S Markus

NEUROLOGY | LIPPINCOTT WILLIAMS & WILKINS | Published : 2019

Abstract

OBJECTIVE: To identify novel genetic associations with white matter hyperintensities (WMH). METHODS: We performed a genome-wide association meta-analysis of WMH volumes in 11,226 individuals, including 8,429 population-based individuals from UK Biobank and 2,797 stroke patients. Replication of novel loci was performed in an independent dataset of 1,202 individuals. In all studies, WMH were quantified using validated automated or semi-automated methods. Imputation was to either the Haplotype Reference Consortium or 1,000 Genomes Phase 3 panels. RESULTS: We identified a locus at genome-wide significance in an intron of PLEKHG1 (rs275350, β [SE] = 0.071 [0.013]; p = 1.6 × 10-8), a Rho guanine n..

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Grants

Awarded by British Heart Foundation Programme Grant


Awarded by British Heart Foundation Immediate Research Fellowship


Awarded by NIH/NINDS


Awarded by NIH


Awarded by American Heart Association/Bugher Foundation Centers for Stroke Prevention Research


Funding Acknowledgements

This work was supported by a British Heart Foundation Programme Grant (RG/16/4/32218). Hugh Markus is supported by a National Institute for Health Research (NIHR) Senior Investigator award, and his work is supported by the Cambridge Universities NIHR Comprehensive Biomedical Research Centre. Loes Rutten-Jacobs was supported by a British Heart Foundation Immediate Research Fellowship (FS/15/61/31626). Natalia S. Rost is supported in part by NIH/NINDS R01NS086905 and R01NS082285. The MGH WMH study was supported by the NIH (K23NS064052; N. R.), American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N), and Deane Institute for Integrative Study of Atrial Fibrillation and Stroke. Robin Lemmens is a senior clinical investigator of FWO Flanders.