Original ContributionsAssociation Study of GABAA α2 Receptor Subunit Gene Variants in Antipsychotic-Associated Weight GainZai, Clement C.H. PhD*†; Tiwari, Arun K. PhD*; Chowdhury, Nabilah I. BSc*; Brandl, Eva J. MD*‡; Shaikh, Sajid A. BSc*; Freeman, Natalie MSc*; Lieberman, Jeffrey A. MD§; Meltzer, Herbert Y. MD║; Müller, Daniel J. MD, PhD*†; Kennedy, James L. MD*†Author Information From the *Neurogenetics Section, Centre for Addiction and Mental Health; †Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; ‡Department of Psychiatry and Psychotherapy, Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany; §Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, Lieber Center for Schizophrenia Research, New York Presbyterian Hospital & Columbia University Medical Center, New York, NY; and ║Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL. Received May 6, 2014; accepted after revision November 3, 2014. Reprints: Daniel J. Müller, MD, PhD, and James L. Kennedy, MD, 250 College Street, Toronto, Ontario, Canada M5T1R8 (e-mail: firstname.lastname@example.org; email@example.com). Drs Müller and Kennedy are co-senior authors. Supported by operating grants from the Canadian Institutes of Health Research (CIHR) to D.J.M. (Genetics of antipsychotics-induced metabolic syndrome, MOP 89853) and J.L.K. (MOP 115097); National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Investigator Award to D.J.M.; NARSAD Young Investigator Award to A.K.T. and C.C.Z.; CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia to D.J.M.; Ontario Mental Health Foundation (OMHF) New Investigator Fellowship to D.J.M.; OMHF Scholarship to N.I.C.; and fellowship funding from the American Foundation for Suicide Prevention and Eli Lilly to C.C.Z. Journal of Clinical Psychopharmacology: February 2015 - Volume 35 - Issue 1 - p 7-12 doi: 10.1097/JCP.0000000000000261 Buy Metrics Abstract Schizophrenia treatment has been hampered by undesirable adverse effects, including weight gain and associated complications. Recent candidate gene studies have been exploring the appetite regulation pathways in antipsychotic-associated weight gain (AAWG) with some promising leads. Genome-wide association studies of obesity have pointed to a number of potential candidate genes, such as MC4R, that were later found to be shared with AAWG. GABAA α2 receptor subunit (GABRA2) was another potential candidate gene for obesity from genome-wide association studies; however, it has not been explored in AAWG. We examined 9 single nucleotide polymorphisms across the GABRA2 gene. Prospective weight change was assessed for a total of 160 schizophrenia patients of European ancestry. The rs279858 marker was associated with percent weight change, with the patients homozygous for the TT genotype experiencing higher percentage weight gain on average than the C allele carriers (P = 0.009). When we performed the analysis considering each clinical site using a meta-analytic method, the results remained statistically significant (P = 1.4e−4). These findings became even more significant when we considered only patients taking clozapine or olanzapine, the 2 medications with higher risk for weight gain (P < 1e−10). GABRA2 genetic variants may play a role in predicting AAWG. However, replication in larger and independent samples is required. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.