Association studies of variants in MEIS1, BTBD9, and MAP2K5/SKOR1 with restless legs syndrome in a US population

Sleep Med. 2011 Sep;12(8):800-4. doi: 10.1016/j.sleep.2011.06.006.


Background: A genome-wide association study (GWAS) identified significant association between variants in MEIS1, BTBD9, and MAP2K5/SKOR1 and restless legs syndrome (RLS). However, many independent replication studies are needed to unequivocally establish a valid genotype-phenotype association across various populations. To further validate the GWAS findings, we investigated three variants, rs2300478 in MEIS1, rs9357271 in BTBD9, and rs1026732 in MAP2K5/SKOR1 in 38 RLS families and 189 RLS patients/560 controls from the US for their association with RLS.

Method: Both family-based and population-based case-control association studies were carried out.

Results: The family-based study showed that SNP rs1026732 in MAP2K5/SKOR1 was significantly associated with RLS (P=0.01). Case-control association studies showed significant association between all three variants and RLS (P=0.0001/OR=1.65, P=0.0021/OR=1.59, and P=0.0011/OR=1.55 for rs2300478, rs9357271, and rs1026732, respectively).

Conclusion: Variants in MEIS1, BTBD9, and MAP2K5/SKOR1 confer a significant risk of RLS in a US population.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics*
  • Humans
  • MAP Kinase Kinase 5 / genetics*
  • Male
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics*
  • Nerve Tissue Proteins
  • Restless Legs Syndrome / epidemiology
  • Restless Legs Syndrome / genetics*
  • Risk Factors
  • Transcription Factors / genetics*
  • United States / epidemiology


  • BTBD9 protein, human
  • Homeodomain Proteins
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Transcription Factors
  • MAP Kinase Kinase 5
  • MAP2K5 protein, human