Background Weight gain is one of the major problems in patients using antipsychotic medication, leading to relevant morbidities and reduced compliance to pharmacotherapy. Recently, an association has been reported between a single nucleotide polymorphism (rs1455832) of the roundabout axon guidance receptor, homolog 1 (ROBO1) gene and body mass index (BMI) in persons younger than 30 years. The aim of this study is to investigate the association between BMI and rs1455832 in patients with a psychotic disorder using antipsychotics. Methods A cross-sectional design was used in a pooled sample of Caucasian psychiatric patients obtained from three comparable Dutch psychiatric populations. Patients were eligible for inclusion in this study if they met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a nonaffective psychotic disorder, were 18 years or older, and used one or more antipsychotics. Genotyping was performed according to standard protocols. Linear (for BMI) and logistic (for obesity, defined as BMI>30) regression analyses, corrected for age and sex, were applied in the statistical analyses. Results A total of 435 patients were included in this association analyses. The rs1455832 polymorphism studied was significantly associated with BMI and obesity in female patients. Female patients had a statistically significant (P=0.025) decrease of 1.76 kg/m(2) in BMI values per C allele. In contrast to female patients, this association was not exhibited in male patients. Conclusion The rs1455832 polymorphism may play a role in inducing obesity in female patients using antipsychotics. Psychiatr Genet 21:202-207 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.