Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies

Publication date: Available online 7 April 2016 Source:The Lancet Neurology Author(s): Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) ConsortiumStroke Genetics Network (SiGN)International Stroke Genetics Consortium (ISGC) Background Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. Methods For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10−6) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-...
Source: The Lancet Neurology - Category: Neurology Source Type: research