Association between restless legs syndrome and CLOCK and NPAS2 gene polymorphisms in schizophrenia

Jin Sook Jung, Heon Jeong Lee, Chul Hyun Cho, Seung Gul Kang, Ho Kyoung Yoon, Young Min Park, Joung Ho Moon, Hee Jung Yang, Hyun Mi Song, Leen Kim

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Previous studies have suggested that there is a genetic basis to restless legs syndrome (RLS) development. Occurrence of antipsychotic-induced RLS could also be due to differences in genetic susceptibility. We investigated whether CLOCK and NPAS2 gene polymorphisms are associated with RLS in schizophrenic patients on antipsychotics because RLS symptoms usually manifest during the evening and night. We assessed symptoms of RLS in 190 Korean schizophrenic patients on antipsychotics and divided the subjects into two groups according to the International Restless Legs Syndrome Study Group diagnostic criteria: (i) subjects who met all the criteria and (ii) the remaining subjects who did not meet all the criteria. We found a significant difference in the number of subjects with different genotype and allele carrier frequencies for the CLOCK gene (rs2412646) between the two groups (p = 0.031 and 0.010, respectively). Distribution of CLOCK haplotypes (rs2412646-rs1801260) was significantly different between schizophrenic patients with and without RLS (p = 0.021). However, the distributions of allelic, genotypic, and haplotypic variants of NPAS2 (rs2305160 and rs6725296) were not significantly different between the two groups. Our results suggest that CLOCK polymorphisms are associated with increased susceptibility of schizophrenic patients to RLS. We hypothesize that RLS in schizophrenia patients treated with antipsychotics may be a very mild akathisia that manifests during the night and is under control of circadian oscillation.

Original languageEnglish
Pages (from-to)838-844
Number of pages7
JournalChronobiology International
Issue number7
Publication statusPublished - 2014 Aug

Bibliographical note

Funding Information:
This study was supported by the Korea Health 21 R&D Project of the Ministry of Health & Welfare (HI11C1901), the National Research Foundation of Korea (2012M3A9C7050135) (H.-J. L.) and the intramural grant from Korea University (L. K.).


  • Antipsychotics
  • CLOCK gene
  • Circadian rhythm
  • Restless legs syndrome

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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