Genetic associations of periodic limb movements of sleep in the elderly for the MrOS sleep study

Sleep Med. 2015 Nov;16(11):1360-1365. doi: 10.1016/j.sleep.2015.07.017. Epub 2015 Aug 11.

Abstract

Objective: The objective of this study was to assess the relationship between single-nucleotide polymorphisms associated with restless legs syndrome and periodic limb movements of sleep in a population cohort of elderly individuals.

Methods: Single-nucleotide polymorphisms previously associated with periodic limb movements of sleep or restless legs syndrome were analyzed in 2356 white male participants in the Osteoporotic Fractures in Men Sleep Study cohort. The associations between single-nucleotide polymorphisms and polysomnographically measured periodic limb movement index ≥15 were examined with logistic regression adjusted for age, ancestry markers, and periodic limb movements of sleep risk factors.

Results: Of the men in this cohort, 61% had a periodic limb movement index ≥15. Significant associations were observed between a periodic limb movement index ≥15 and the number of risk alleles for the two BTBD9 single-nucleotide polymorphisms (rs9357271[T], odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.20-1.58; and rs3923809[A], OR = 1.43, 95% CI 1.26-1.63), one of the MEIS1 single-nucleotide polymorphisms (rs2300478[G], OR = 1.31, 95% CI 1.14-1.51) and the mitogen-activated protein kinase kinase 5 (MAP2K5)/Ski family transcriptional corepressor 1 (SKOR1) single-nucleotide polymorphism (rs1026732[G], OR = 1.16, 95% CI 1.02-1.31). In a multivariable model controlling for each of the two MEIS1 single-nucleotide polymorphisms, the rs6710341[A] single-nucleotide polymorphism became a significant risk allele (OR = 1.59, 95% CI 1.26-2.00).

Conclusions: Our findings confirm an association between the BTBD9, MEIS1, and MAP2K5/SKOR1 single-nucleotide polymorphisms and periodic limb movements of sleep in an elderly cohort not selected for the presence of restless legs syndrome.

Keywords: BTBD9; MEIS1; Periodic limb movements of sleep; Restless legs syndrome; Single-nucleotide polymorphism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Cohort Studies
  • Gene Frequency
  • Homeodomain Proteins / genetics*
  • Humans
  • MAP Kinase Kinase 5 / genetics*
  • Male
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics*
  • Nerve Tissue Proteins
  • Nocturnal Myoclonus Syndrome / epidemiology
  • Nocturnal Myoclonus Syndrome / genetics*
  • Polymorphism, Single Nucleotide*
  • Polysomnography / methods
  • Restless Legs Syndrome / epidemiology
  • Restless Legs Syndrome / genetics*
  • Risk Factors
  • Sleep / genetics
  • Transcription Factors / genetics*

Substances

  • 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