Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.
ABSTRACT Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.
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ABSTRACT: Heavy metals, various pesticide and herbicides are implicated as risk factors for human health. Paraquat, maneb, and rotenone, carbamate, and organophosphorous insecticides are examples of toxicants for which acute and chronic exposure are associated with multiple neurological disorders including Parkinson's disease. Nevertheless, the role of pesticide exposure in neurodegenerative diseases is not clear-cut, as there are inconsistencies in both the epidemiological and preclinical research. The aim of this short review is to show that at least, some of the inconsistencies are related to individual differences in susceptibility to the effects of neurotoxicants, individual differences that can be traced to the genetic constitution of the individuals and animals studies, i.e., host-based susceptibility.Frontiers in Genetics 09/2014; 5:327.
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ABSTRACT: Obstructive sleep apnea (OSA) is a highly heterogeneous sleep disorder, and increasing evidence suggests that genetic factors play a role in the etiology of OSA. Airway muscle dysfunction might promote pharyngeal collapsibility, mutations or single nucleotide polymorphisms (SNPs) in the delta-sarcoglycan (SCGD) gene associated with muscle dysfunction. To evaluate if SCGD gene SNPs are associated with OSA, 101 individuals without OSA and 97 OSA patients were recruited randomly. The genotype distributions of SNPs (rs157350, rs7715464, rs32076, rs13170573 and rs1835919) in case and control populations were evaluated. The GG, GC and CC genotypes of rs13170573 in control and OSA groups were 51.5% and 37.1%, 36.6% and 35.1%, and 11.9% and 27.8%, respectively. Significantly fewer OSA patients possessed the GG genotype and significantly more possessed the CC genotype compared with controls. Further multivariate logistic regression analysis showed that the CC genotype was an independent risk factor for OSA, with an odds ratio (OR) of 2.17 (95% confidence interval [CI]: 1.19-6.01). Other factors, such as age ≥50 years, male gender, body mass index (BMI) ≥25 kg/m2, low-density lipoprotein cholesterol (LDL-C) level ≥3.33 mg/dL, smoking and hypertension, were also independent risk factors for OSA in our multivariate logistic regression model.PLoS ONE 12/2014; 9(12):e114160. · 3.53 Impact Factor
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ABSTRACT: To evaluate the association between white matter lesion (WML) volume, silent infarcts and restless legs syndrome (RLS) in a population-based study of elderly individuals. Cross-sectional study. Population-based Three-City study. 1035 individuals from the Dijon, France, centre of the Three-City study who had available information on volume of WMLs from MRIs and who answered questions about the prevalence of RLS. Prevalence of RLS. WML volume was measured using an automated tissue segmentation method. Logistic regression was used to evaluate adjusted associations between tertiles of WML volume and RLS and between silent infarcts and RLS. 218 individuals (21.1%) were determined to have RLS. Compared with those in the first tertile of WML volume, individuals in the second tertile (OR=1.09; 95% CI 0.75 to 1.60) or third tertile (OR=1.17; 95% CI 0.79 to 1.74) did not have an increased prevalence of RLS. We also did not observe associations between the volume of deep or periventricular WML and RLS; nor did we observe an association between silent brain infarcts and RLS (OR=0.74; 95% CI 0.40 to 1.39). These findings were not modified by age or gender. Higher volume of WML and the presence of silent infarcts were not associated with an increased prevalence of RLS in this population-based cohort of elderly individuals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.BMJ Open 11/2014; 4(11):e005938. · 2.06 Impact Factor