Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest genome-wide association study (GWAS) in IS recovery to date.
Methods and Results: A 12-cohort, two-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent IS cases. Functional outcome was recorded using 3-month modified Rankin Scale (mRS). Analyses were adjusted for confounders such as discharge NIHSS. A gene-based burden test was performed. The discovery phase (n=1,225) was followed by open (n=2,482) and stringent joint-analyses (n=1,791). Those cohorts with mRS recorded at timepoints other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, beta=0·40, p=1·70x10-9).
Conclusions: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.