Exome-wide association study identified genetic variants contributing to the risk of cerebral palsy

Abstract Cerebral palsy (CP) is the most common physical disability in childhood that results from the interaction of environmental and genetic factors. Yet in many patients, the etiology remains unknown. We identified significant association at rs3131787 within the human leukocyte antigen (HLA) region using two-stage association study between 1,090 CP cases and 1,100 controls. Fine mapping of the HLA region indicated that the carrier frequency of HLA-B*13:02 was significantly higher in CP, particularly in CP without preterm birth, low birth weight, birth asphyxia or periventricular leukomalacia (PVL). DRB1*07:01/DQA1*02:01 was also significantly enriched in CP and more specifically in dyskinetic type. Additionally, significant enrichment of carrier frequency was detected for HLA-A*32:01 in CP with either preterm birth or low birth weight and for HLA-B*27:05 in CP with birth asphyxia. These data suggest that immune dysregulation resulting from immunogenetic variants or environmental exposures may underlie the pathogenesis of CP.