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A JAX-led study published today in @cellpress.bsky.social of more than 5,000 people is challenging long-held assumptions about cerebral palsy genetics. 🧬🧪

Only a fraction of the hundreds of genes previously associated with cerebral palsy are strongly linked to this condition, according to a new study of data from more than 5,000 people led by researchers from The Jackson Laboratory (JAX).

The findings suggest cerebral palsy may be better described as a collection of symptoms that can occur in many different conditions because of genetic variants and environmental factors—not a single disease with genetic causes. The study appears today in the American Journal of Human Genetics.

Cerebral palsy (CP) is the most common motor disability in children, with up to 10,000 babies diagnosed in the United States every year. Unlike many other neuromotor diseases found in children, CP is nonprogressive, meaning that it does not worsen over time.

With rehab and PT, many patients can see improvements in their symptoms. While it has largely been linked to prematurity, temporary loss of oxygen to the brain, or other events at birth, research over the past decade has suggested that genetic factors contribute to CP in many children.

This study challenges some of those assumptions. The team examined genetic evidence from 21 studies involving 5,440 people diagnosed w/CP. Those studies reported potentially causal variants in a total of 515 genes. The new analysis found a statistically significant association with CP for only 89.

The team also conducted whole-genome sequencing on 460 children from 453 families who had been diagnosed with CP and treated at Shriners Children’s hospitals around the U.S.

Genetic variants classified as pathogenic or likely pathogenic were identified in 70 families, involving 60 different genes. Only 16 of those 60 genes overlapped with genes that showed statistically significant evidence of association in the authors’ analysis of previously published studies.

The analysis does not rule out a true association of the remaining genes with CP, the authors said. It shows that sufficient evidence does not exist to establish a statistically significant association.

Further research will focus on building larger patient cohorts, conducting prospective studies of clinical utility and cost-effectiveness, and improving the accessibility of genomic and clinical data.

Read the full paper in @cellpress.bsky.social www.cell.com/ajhg/fulltex...