Back to Search
Start Over
A Genetic Risk Factor for Periodic Limb Movements in Sleep
- Source :
- New England Journal of Medicine. 357:639-647
- Publication Year :
- 2007
- Publisher :
- Massachusetts Medical Society, 2007.
-
Abstract
- The restless legs syndrome (RLS) is a common neurologic disorder characterized by an irresistible urge to move the legs. It is a major cause of sleep disruption. Periodic limb movements in sleep are detectable in most patients with RLS and represent an objective physiological metric.To search for sequence variants contributing to RLS, we performed a genomewide association study and two replication studies. To minimize phenotypic heterogeneity, we focused on patients with RLS who had objectively documented periodic limb movements in sleep. We measured serum ferritin levels, since iron depletion has been associated with the pathogenesis of RLS.In an Icelandic discovery sample of patients with RLS and periodic limb movements in sleep, we observed a genomewide significant association with a common variant in an intron of BTBD9 on chromosome 6p21.2 (odds ratio, 1.8; P=2x10(-9)). This association was replicated in a second Icelandic sample (odds ratio, 1.8; P=4x10(-4)) and a U.S. sample (odds ratio, 1.5; P=4x10(-3)). With this variant, the population attributable risk of RLS with periodic limb movements was approximately 50%. An association between the variant and periodic limb movements in sleep without RLS (and the absence of such an association for RLS without periodic limb movements) suggests that we have identified a genetic determinant of periodic limb movements in sleep (odds ratio, 1.9; P=1x10(-17)). Serum ferritin levels were decreased by 13% per allele of the at-risk variant (95% confidence interval, 5 to 20; P=0.002).We have discovered a variant associated with susceptibility to periodic limb movements in sleep. The inverse correlation of the variant with iron stores is consistent with the suspected involvement of iron depletion in the pathogenesis of the disease.
- Subjects :
- Genetic Markers
Male
medicine.medical_specialty
Genotype
Nerve Tissue Proteins
Polymorphism, Single Nucleotide
Linkage Disequilibrium
Nocturnal Myoclonus Syndrome
Physical medicine and rehabilitation
Risk Factors
Restless Legs Syndrome
mental disorders
medicine
Humans
Genetic Predisposition to Disease
Restless legs syndrome
Risk factor
Genome, Human
Genetic heterogeneity
business.industry
Case-control study
Iron Deficiencies
General Medicine
Odds ratio
medicine.disease
Sleep in non-human animals
Surgery
BTBD9
Case-Control Studies
Ferritins
Chromosomes, Human, Pair 6
Female
business
Transcription Factors
Subjects
Details
- ISSN :
- 15334406 and 00284793
- Volume :
- 357
- Database :
- OpenAIRE
- Journal :
- New England Journal of Medicine
- Accession number :
- edsair.doi.dedup.....6252151fbd095d730d8486fff0b58546