Translational Study of Copy Number Variation of Genomic Dna in Schizophrenia

Copy number variations of genomic DNA (CNV) is a new type of genetic variation, including duplication and deletion, which range from 1 kb to several hundreds of kb. Accumulating evidence indicates CNVs are associated with mental disorders, especially autism spectrum disorder and schizophrenia. However, most previous studies lack enough statistical power due to limited sample size. In 2017, CNV and Schizophrenia Working Groups of Psychiatric Genomic Consortium published the results of CNV analysis between 21,094 schizophrenia patients and 20,227. They found CNVs at eight genetic loci reached the genome-wide signficancce, including 1q21.1, 2p16.3, 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. This study has enough statistical power, thus, these eight CNVs can be considered pathogenic CNVs of schizophrenia. Chromosomal microarray analysis is the gentic tool to detect CNV. However, it is needs special equaipment and is expensive, which limit its clinical utility. The goal of this study is to use real-time quantitative PCR (RT-qPRC) of genomic DNA as an alternative to screen eight pathogenic CNVs. Positive cases will then be verified by chromosomal microarray analysis. We plan to accomplishe this study in two years. In the first year, we will choose genes encompassed by these eight pathogenic CNVs as representative genes and find the optimal RT-qPCR conditions that can accurately detect copy number changes in eight pathogenic CNV loci. In the second year, we will screen 500 schizophrenia patietns using the optimal RT-qPCR method as the screening method. Positive cases from the screening test will be validated using chromosomal microarray analysis. We expect the study will uncover the prevalence of eight pathogenic CNVs in our population and facilitate the establishment of a genetic testing for schizophrenia.

Project ID:PC10907-0866
External Project ID:MOST109-2314-B182-044-MY2