The following is a summary of “Genome-Wide Association Studies of 3 Distinct Recovery Phenotypes in Mild Ischemic Stroke,” published in the January 2024 issue of Neurology by Aldridge et al.
Stroke genetics raced ahead, but recovery research lagged, hobbled by a single, imprecise modified Rankin Scale (mRS) score that muddles biology with psychosocial factors and lumps diverse processes into one blunt measure.
Researchers conducted a retrospective study to leverage the NIH Stroke Scale (NIHSS) and its sub-scores within Genome-Wide Association Studies (GWASs), probing how different post-stroke recovery patterns relate to genetic variations.
They assessed changes in cognition, motor, and global impairments over 2 years using specific Vitamin Intervention for Stroke Prevention cohort measures. Genotyped participants with NIHSS > 0 at randomization were included, excluding recurrent strokes during the trial. A GWAS model predicted score changes, considering the initial score, age, sex, treatment group, and the first 5 ancestry principal components, with participants as a random effect.
The results showed 1,270 participants (64% male) with a median NIHSS score of 2 (IQR 1–3) and median age of 68 (IQR 59–75) years. At randomization, 20% had cognitive deficits (NIHSS Cog-4 score >0), and 70% had ≥1 motor deficits (impairment score >1). At 2 years, these percentages improved to 7.2% with cognitive deficits and 30% with motor deficits. GWAS revealed novel suggestive gene-impairment associations (P<5e-6) for cognition (CAMK2D, EVX2, LINC0143, PTPRM, SGMS1, and SMAD2), motor (ACBD6, KDM4B, MARK4, PTPRS, ROBO1, and ROBO2), and global (MSR1 and ROBO2) impairments.
They concluded that granular outcome measures and longitudinal trials unlocked novel genes linked to chronic stroke recovery, highlighting the power of precision in uncovering genetic drivers.