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Genetic association between RGS1 and internalizing disorders

Hettema, John M.a; An, Seon-Sookd; van den Oord, Edwin J.C.G.c; Neale, Michael C.a,b; Kendler, Kenneth S.a,b; Chen, Xiangninga

doi: 10.1097/YPG.0b013e32835d7048
Original Articles

Objective: Quantitative trait loci identified in animal models provide potential candidate susceptibility loci for human disorders. In this study, we investigated whether internalizing disorders (anxiety disorders, major depression, and neuroticism) were associated with a region on human chromosome 1 syntenic with a quantitative trait locus for rodent emotionality.

Methods: We genotyped 31 single-nucleotide polymorphisms in genes located on chromosome 1q31.2 in a two-stage association study of 1128 individuals chosen for a high or a low genetic risk for internalizing disorders from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.

Results: None of the individual single-nucleotide polymorphisms showed consistent association across stages. A four-marker haplotype in the regulator of G-protein signaling 1 gene (RGS1) was significantly associated with decreased internalizing risk in both stages, whereas another showed a nominal association with a higher risk.

Conclusion: Our data suggest that markers in the RGS1 gene might be in linkage disequilibrium with a protective allele that reduces the risk of anxiety and depressive disorders.

Departments of aPsychiatry

bHuman Genetics, Virginia Institute for Psychiatric and Behavioral Genetics

cDepartment of Pharmacy, Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, Virginia

dGeneral Studies and Basic Education, Northeast Wisconsin Technical College, Green Bay, Wisconsin, USA

Correspondence to John M. Hettema, MD, PhD, Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, PO Box 980126, Richmond, VA 23298-0126, USA Tel: +1 804 828 8592; fax: +1 804 828 1471; e-mail: jhettema@vcu.edu

Received February 14, 2012

Accepted September 1, 2012

© 2013 Lippincott Williams & Wilkins, Inc.