Detection of Parent-of-Origin Effects for the Variants Associated With Behavioral Disinhibition in the MCTFR Data

Front Genet. 2022 Apr 26;13:831685. doi: 10.3389/fgene.2022.831685. eCollection 2022.


Behavioral disinhibition is one of the important characteristics of many mental diseases. It has been reported in literature that serious behavioral disinhibition will affect people's health and greatly reduce people's quality of life. Meanwhile, behavioral disinhibition can easily lead to illegal drug abuse and violent crimes, etc., which will bring great harm to the society. At present, large-scale genome-wide association analysis has identified many loci associated with behavioral disinhibition. However, these studies have not incorporated the parent-of-origin effects (POE) into analysis, which may ignore or underestimate the genetic effects of loci on behavioral disinhibition. Therefore, in this article, we analyzed the five phenotypes related to behavioral disinhibition in the Minnesota Center for Twin and Family Research data (nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance use related behavioral disinhibition), to further explore the POE of variants on behavioral disinhibition. We applied a linear mixed model to test for the POE at a genome-wide scale on five transformed phenotypes, and found nine SNPs with statistically significant POE at the significance level of 5 × 10-8. Among them, SNPs rs4141854, rs9394515, and rs4711553 have been reported to be associated with two neurological disorders (restless legs syndrome and Tourette's syndrome) which are related to behavioral disinhibition; SNPs rs12960235 and rs715351 have been found to be associated with head and neck squamous cell carcinoma, skin cancer and type I diabetes, while both SNPs have not been identified to be related to behavioral disinhibition in literature; SNPs rs704833, rs6837925, rs1863548, and rs11067062 are novel loci identified in this article, and their function annotations have not been reported in literature. Follow-up study in molecular genetics is needed to verify whether they are surely related to behavioral disinhibition.

Keywords: Minnesota Center for Twin and Family Research data; behavioral disinhibition; genome-wide association study; parent-of-origin effects; rank-based inverse normal transformation.