The genetic etiology of periodic limb movement in sleep.
Sleep
; 46(4)2023 04 12.
Article
em En
| MEDLINE
| ID: mdl-35670608
ABSTRACT
STUDY OBJECTIVES:
Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects.METHODS:
The MrOS study and Wisconsin Sleep Cohort Study (Nâ =â 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization.RESULTS:
We found 2 independent loci were significantly associated with PLMS rs113851554 (pâ =â 3.51â ×â 10-12, ßâ =â 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (pâ =â 3.06â ×â 10-22, ßâ =â 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS.CONCLUSIONS:
Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome das Pernas Inquietas
/
Distúrbios do Início e da Manutenção do Sono
Tipo de estudo:
Clinical_trials
/
Etiology_studies
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Observational_studies
/
Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Sleep
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos