RORA polymorphism interacts with childhood maltreatment in determining anxiety sensitivity by sex: a preliminary study in healthy young adults
Jung-Ah Min 1, Heon-Jeong Lee 2, Seung-Hwan Lee 3, Young-Min Park 3, Seung-Gul Kang 4, Yong-Gyu Park 5, Jeong-Ho Chae 6*
1Department of Psychiatry, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Kore, 2Department of Psychiatry and Division of Brain Korea 21 Biomedical Science, Korea University, College of Medicine, Republic of Korea, 3Department of Psychiatry, Inje University College of Medicine, Republic of Korea, 4Department of Psychiatry, Gachon University, School of Medicine, Republic of Korea, 5Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea , 6Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Received: November 25, 2016; Revised: February 2, 2017; Accepted: February 2, 2017; Published online: February 2, 2017.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: Recent studies have reported associations of retinoid-related orphan receptor alpha (RORA) gene single nucleotide polymorphisms (SNPs) with depression and anxiety disorders. Based on these, we attempt to test whether RORA polymorphism is associated with anxiety sensitivity (AS), the intermediate phenotype of depression and anxiety disorders. Considering gene-environment interactions and sex differences in AS, childhood maltreatment (CM) and sex were considered as confounders.
Methods: Two-hundred and five healthy young Korean adults (F:M = 98:107, age = 23.0 ± 3.2 years) completed genotyping for the RORA SNP rs11071547, as well as measures for AS and CM. Generalized linear models were used to examine the main and interaction effects of RORA genotype, CM, and sex in determining AS.
Results: The main effect of RORA polymorphisms was not found (p = 0.760) whereas the main effect of CM and interaction effects among sex, genotype, and maltreatment were significant on AS. In separate analyses by sex, the interaction effect between RORA genotype and maltreatment was significant only in males (p < 0.001). In females, the main effects of genotype and CM were significant (both were p < 0.001), in which both a history of CM and C genotype tended to be associated with higher AS.
Conclusion: The association between RORA polymorphism and AS might differ by sex. The interaction between RORA polymorphism and CM was significant only in males whereas RORA genotype and CM independently associated with AS in females. Further studies are encouraged to confirm the relationship between RORA polymorphism and AS.
Keywords: Gene-environment interaction, Retinoid acid receptor-related orphan receptor alpha (RORA), Childhood trauma, Sex, Anxiety sensitivity


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