Lack of Association between Genetic Risk Loci for Restless Legs Syndrome and Multimorbidity.
OBJECTIVE
Multimorbidity is a risk factor for incident restless legs syndrome (RLS). In this relationship, the potential role of known genetic risk loci for RLS has not been studied. Our aim was to evaluate whether carriers of specific RLS risk alleles have higher comorbidity burden than noncarriers.


METHODS
The Dortmund Health Study (DHS) and the Study of Health in Pomerania (SHIP) are two independent cohort studies in Germany based on age-stratified, random samples drawn from the respective population registers. DHS included 1,312 subjects and SHIP included 4,308 subjects. RLS status was assessed according to the RLS standard minimal criteria. A comorbidity index was calculated by summing the scores of the following conditions: diabetes, hypertension, myocardial infarction, obesity, stroke, cancer, renal disease, anemia, depression, thyroid disease, and migraine. Thirteen single nucleotide polymorphisms (SNP) previously associated with elevated risk of RLS were genotyped. Analyses were carried out on the pooled sample of the two studies.


RESULTS
The mean age was 50.4 ± 15.9 y, and the proportion of women was 51.4%. The mean number of comorbid conditions was 1.5 ± 1.3. In multivariable regression, the mean number of comorbidities was not significantly different between carriers of any of the RLS risk alleles and noncarriers either in the total pooled sample or in those having RLS symptoms.


CONCLUSIONS
Based on these results it is unlikely that known genetic risk factors for RLS would lead to increased multimorbidity.
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
András
A
Szentkirályi
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.|German Centre for Cardiovascular Research, Partner site Greifswald, Germany.
Henry
H
Völzke
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.|German Centre for Neurodegenerative Diseases (DZNE), Germany.
Wolfgang
W
Hoffmann
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.|Department of Neurology, Technische Universität München, Munich, Germany.|Department of Neurology and Neurosciences, Stanford Center for Sleep Medicine and Sciences, Stanford University, Palo Alto, CA.
Julianne
J
Winkelmann
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Klaus
K
Berger
D000483:Alleles; D000740:Anemia / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D007674:Kidney Diseases / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000453:epidemiology / Q000235:genetics; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012148:Restless Legs Syndrome / Q000453:epidemiology* / Q000235:genetics*; D020521:Stroke / Q000453:epidemiology / Q000235:genetics; D013959:Thyroid Diseases / Q000453:epidemiology / Q000235:genetics
multimorbidity; restless legs syndrome; risk alleles