A set of 14 genetic variants initially identified from a genome-wide search and replicated in other samples could distinguish the age at onset (AAO) in schizophrenia patients who had a co-affected sibling in Taiwan. Network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson’s disease and schizophrenia research. These are the findings of a genetic study on patients recruited from multiplex families led by Dr. Wei J. Chen, dean and distinguished professor at National Taiwan University College of Public Health, with his doctoral student Ms. Annemarie L. Woolston as first author. This study was published online on July 25, in Scientific Reports.
An earlier AAO has been associated with greater genetic loadings in schizophrenia. “Our strategy is to make use of this feature by examining patients coming from multiplex families, i.e., at least two affected individuals in a nuclear family,” said Ms. Woolston. She further pointed out, “by means of a case-only approach, we’d be able to search for another class of genes involved in the clinical manifestations of the illness, i.e., modifier genes.”
According to Dr. Chen, corresponding author of the study, “we found a genetic risk scores consisting of 14-SNPs derived from the initial GWAS subsample, 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO selected from 557 multiplex families, could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands.” The team then examined another 132 patients with an earlier AAO and 158 patients with a later AAO. They found a significant trend in the 14-SNP GRS among those unrelated probands from four family groups with the earliest, earlier, later, and latest AAO.
When these 14 SNPs were subjected to network analysis, the results revealed five significant gene networks, including a larger network centering on PARK2 and four small networks consisting of N4BP2, and KCNIP4, ADGRL2, and NCOA7, respectively. Ms. Woolston highlighted the finding about PARK2, because “mutations in PARK2 at 6q25.2-q27 have been intensively studied in Parkinson’s disease, especially those with early onset.” This finding is consistent with the increasing evidence pointing to a potential overlapping pathogenesis between Parkinson’s disease and schizophrenia since they had opposite dopaminergic dysfunctions, similar psychotic symptoms, and shared some gene networks. Future investigation of these AAO-modifying genetic loci may help further illuminate the pathogenesis of schizophrenia.
[Photo: Ms. Annemarie L. Woolston (left) and Dr. Wei J. Chen (right)]