Genome-Wide Association Study Identifies Genetic Risk Factors for Spastic Cerebral Palsy

Neurosurgery. 2021 Aug 16;89(3):435-442. doi: 10.1093/neuros/nyab184.


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 (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.

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.

Keywords: Cerebral palsy; GWAS; Genetics; Spasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebral Palsy* / genetics
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study*
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors