Additional genetic defects outside commonly deleted region in 22q11.2 deletion with psychosis; a prospect for identifying novel schizophrenia candidate genes

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860954
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: SHABEESH BALAN 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (70721588)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 22q11.2 deletion / Schizophrenia / SNX31 / CLV2 / EFCAB11 / KAT8 / APOH

Outline of Final Research Achievements

22q11.2 deletion is a prominent risk factor for developing schizophrenia, with varying penetrance. This suggests polygenic mechanisms requiring additional genomic variants for disease manifestation. We aimed to decipher the role of genetic defects outside the 22q11.2 region in increasing the risk for schizophrenia. We did whole exome sequencing on two subjects with 22q11.2 deletions; one with schizophrenia and other psychosis free. We identified 5 heterozygous variants in genes (3 frameshift: KAT8, APOH and SNX31 and 2 nonsense variants: EFCAB11 and CLVS2) outside the deletion region in 22q11.2 deletion patient with schizophrenia. Although these genes were relevant for neuronal function, interestingly, none of them were reported to be associated with any neurological/psychiatric phenotypes. These results will help in elucidating the variant dose and complex genetic architecture in schizophrenia. Role of these genes in manifestation of psychiatric phenotypes warrant future examination.

Free Research Field

Genetics