Understanding how genetic variants in the oxytocin receptor gene (OXTR) confer the risk of autism spectrum disorder - a genetic and molecular biology analysis

2021 Fiscal Year Annual Research Report

• Project/Area Number: 18K15502
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: LIU XIAOXI 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (20709216)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: OXTR / common variant / autism

Outline of Annual Research Achievements

OXTR is a GPCR that has been known associated with autism, a disease that affects social interaction and language inboxed children. By using NGS, we have previously reported OXTR rare variants in autistic patients and the association study supported the rare variant burden was significantly higher in autism patients compared with healthy controls. In this study. we comprehensively screened rare variants in the oxytocin receptor gene (OXTR)Japanese whole-genome-sequencing (WGS) datasets. We applied several deep learning frameworks to infer the likely transcriptional and epigenetic effects. The rs2254298 has been implicated to be associated with autism and a wide range of psychiatric traits, however, the genetic mechanism remains yet unknown. We identified rs2268494, which is in linkage disequilibrium (D' =1) is likely to be functional critical and influence CTCF binding, and affect the regulate the gene expression of OXTR. We further identified two rare variants in the Japanese population that were predicted to exert significant effects in the promoter region of OXTR. Finally, we utilized the AlphaFold2 program to analyze the possible structural changes caused by coding variants in OXTR which were located in the predicated “polar pocket” sites.