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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364821 | PMC |
| http://dx.doi.org/10.1093/neuros/nyab184 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HighDimMixedModels.jl: Robust high-dimensional mixed-effects models across omics data.
PLoS Comput Biol
January 2025
Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
High-dimensional mixed-effects models are an increasingly important form of regression in which the number of covariates rivals or exceeds the number of samples, which are collected in groups or clusters. The penalized likelihood approach to fitting these models relies on a coordinate descent algorithm that lacks guarantees of convergence to a global optimum. Here, we empirically study the behavior of this algorithm on simulated and real examples of three types of data that are common in modern biology: transcriptome, genome-wide association, and microbiome data.
View Article and Find Full Text PDFA high-quality assembly revealing the PMEL gene for the unique plumage phenotype in Liancheng ducks.
Gigascience
January 2025
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Background: Plumage coloration is a distinctive trait in ducks, and the Liancheng duck, characterized by its white plumage and black beak and webbed feet, serves as an excellent subject for such studies. However, academic comprehension of the genetic mechanisms underlying duck plumage coloration remains limited. To this end, the Liancheng duck genome (GCA_039998735.
View Article and Find Full Text PDFGenome-Wide Association Study and Genomic Predictions for Hydroxycinnamate Concentrations in Maize Stover.
J Agric Food Chem
January 2025
UA MBG-UVIGO, Misión Biológica de Galicia (CSIC), Pazo de Salcedo, Pontevedra 36143, España.
Hydroxycinnamates, like ferulate (FA) and -coumarate (CA), are important components of maize cell walls, which influence pest resistance, ruminal digestibility, and biofuel production. Increasing their concentration has been linked to increased pest resistance, but also may lead to a decrease in nutritional value or bioethanol production efficiency. Therefore, improving forage quality or biofuel production without compromising plant resistance and a thorough understanding of the biosynthesis and deposition of these compounds is necessary, especially in stover, which is the feedstock for second-generation biofuel production and determines animal forage quality.
View Article and Find Full Text PDFCausal relationship between skin microbiota and Hidradenitis suppurativa: a two-sample Mendelian randomization study.
Arch Dermatol Res
January 2025
Coloproctology Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Background: Data from observational and clinical studies indicate an association between skin microbiota and hidradenitis suppurativa (HS). However, the causal relationship between skin microbiota and HS remains to be elucidated.
Methods: We obtained data on skin microbiota and HS from summary statistics of genome-wide association studies and applied Mendelian randomization (MR) statistical methods to assess causality.
Unlabelled: is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!