| Title: | Genome-Wide Association Study Identifies Genetic Risk Factors for Spastic Cerebral Palsy |
| Journal: | Neurosurgery |
| Published: | 7 Jun 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34098570/ |
| DOI: | https://doi.org/10.1093/neuros/nyab184 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364821 |
| Citations: | 12 (6 in last 2 years) as of 8 Aug 2024 |
Publication 5029
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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.</p>
OBJECTIVE: To define the genetic basis of spastic CP.</p>
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.</p>
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.</p>
CONCLUSION: To our knowledge, we perform the first GWAS of spastic CP. Our study indicates that genetic variation contributes to CP risk.</p>
6 Keywords
- Cerebral Palsy
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Polymorphism, Single Nucleotide
- Risk Factors
7 Authors
- Andrew T Hale
- Oluwatoyin Akinnusotu
- Jing He
- Janey Wang
- Natalie Hibshman
- Chevis N Shannon
- Robert P Naftel
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