• Andrew T Hale, Oluwatoyin Akinnusotu, Jing He, Janey Wang, Natalie Hibshman, Chevis N Shannon, and Robert P Naftel.
• Vanderbilt University School of Medicine, Medical Scientist Training Program, Nashville, Tennessee, USA.
• Neurosurgery. 2021 Aug 16; 89 (3): 435442435-442.

BackgroundAlthough many clinical risk factors of spastic cerebral palsy (CP) have been identified, the genetic basis of spastic CP is largely unknown. Here, using whole-genome genetic information linked to a deidentified electronic health record (BioVU) with replication in the UK Biobank and FinnGen, we perform the first genome-wide association study (GWAS) for spastic CP.ObjectiveTo define the genetic basis of spastic CP.MethodsWhole-genome data were obtained using the multi-ethnic genotyping array (MEGA) genotyping array capturing single-nucleotide polymorphisms (SNPs), minor allele frequency (MAF) > 0.01, and imputation quality score (r2) > 0.3, imputed based on the 1000 genomes phase 3 reference panel. Threshold for genome-wide significance was defined after Bonferroni correction for the total number of SNPs tested (P < 5.0 × 10-8). Replication analysis (defined as P < .05) was performed in the UK Biobank and FinnGen.ResultsWe identify 1 SNP (rs78686911) reaching genome-wide significance with spastic CP. Expression quantitative trait loci (eQTL) analysis suggests that rs78686911 decreases expression of GRIK4, a gene that encodes a high-affinity kainate glutamatergic receptor of largely unknown function. Replication analysis in the UK Biobank and FinnGen reveals additional SNPs in the GRIK4 loci associated with CP.ConclusionTo our knowledge, we perform the first GWAS of spastic CP. Our study indicates that genetic variation contributes to CP risk.© Congress of Neurological Surgeons 2021.

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