The BTBD9 gene may be associated with antipsychotic-induced restless legs syndrome in schizophrenia


Correspondence to: H.-J. Lee, MD, PhD, Department of Psychiatry, Anam Hospital, Korea University College of Medicine, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea. E-mail:



A genome-wide association study and several replication studies have shown significant association between BTBD9 gene single nucleotide polymorphisms and restless legs syndrome (RLS). The aim of this study is to investigate the association between the BTBD9 gene polymorphisms and antipsychotic-induced RLS in schizophrenic patients.


Restless legs syndrome symptoms were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group in 190 Korean schizophrenic patients. We genotyped the rs9357271 and rs3923809 polymorphisms of the BTBD9 gene in schizophrenic patients with (n = 96) and without (n = 94) RLS symptoms.


There was a significant difference in the allele frequency (χ2 = 8.14, p = 0.004) of the rs9357271 polymorphism between schizophrenic patients with and without RLS symptoms. Significant genotypic association of this single nucleotide polymorphisms with RLS symptoms was also observed for the dominant model (χ2 = 10.32, p = 0.001) and heterozygous model (χ2 = 10.9, p = 0.001). When we compared the frequencies of the rs3923809–rs9357271 haplotypes between the two groups, the overall haplotype frequencies were significantly different (permuted p = 0.037), and the A-T haplotype was significantly more frequent in the RLS symptom group than in the no RLS symptom group (0.112 vs. 0.041, permuted p = 0.007).


These data suggest that the BTBD9 gene is associated with antipsychotic-induced RLS symptoms in schizophrenic patients. Copyright © 2013 John Wiley & Sons, Ltd.