4.6 Article

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

Journal

SLEEP MEDICINE
Volume 16, Issue 11, Pages 1360-1365

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.sleep.2015.07.017

Keywords

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

Funding

  1. National Institutes of Health
  2. National Institute on Aging (NIA)
  3. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  4. National Center for Advancing Translational Sciences (NCATS)
  5. NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128]
  6. National Heart, Lung, and Blood Institute (NHLBI) [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, R01 HL070839]
  7. NIA [1R01AG030474]

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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 singlenucleotide polymorphisms and periodic limb movements of sleep in an elderly cohort not selected for the presence of restless legs syndrome. (C) 2015 Elsevier B.V. All rights reserved.

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