Genome‐Wide Association Study Identifies Genetic Risk Factors for Spastic Cerebral Palsy. Issue 3 (September 2021)

• Record Type: Journal Article
• Authors: Hale, Andrew T; Akinnusotu, Oluwatoyin; He, Jing; Wang, Janey; Hibshman, Natalie; Shannon, Chevis N; Naftel, Robert P
• Is Part Of: Neurosurgery. Volume 89:Issue 3(2021)
• Publication Date: 2021-09
• Subjects: GWAS -- Genetics -- Cerebral palsy -- Spasticity; Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyab184
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract : BACKGROUND : Although 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. OBJECTIVE : To define the genetic basis of spastic CP. METHODS : Whole‐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 (r 2 ) > 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. RESULTS : We 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. CONCLUSION : To our knowledge, we perform the first GWAS of spastic CP. Our study indicates that genetic variation contributes to CP risk.