Genetic and epidemiological characterization of restless legs syndrome in Québec

Abstract

Currently, a total of 19 genetic loci are associated with the risk for developing RLS. This study aimed to assess these RLS predisposing genetic variants, as well as investigate the epidemiological profile and diagnostic features of individuals with RLS in the Québec population, using an interviewer–administered questionnaire. A total of 18 RLS-associated variants were genotyped in the Québec population-based CARTaGENE cohort. A case–control series consisting of 1,362 RLS cases and 1,379 age-matched unaffected controls was used to conduct a genetic and epidemiological association study that integrated the first four RLS diagnostic features of affected individuals, as well as additional RLS-related questions (e.g. frequency of the symptoms and number of total pregnancies in female). Five RLS-predisposing variants were significantly associated after Bonferroni correction and an additional five variants were nominally associated with RLS (p < 0.05). BTBD9 was the strongest genetic risk factor in our cohort (rs9296249, OR = 1.71, p = 9.57 × 10−10). The patient group that met all four essential diagnostic criteria of RLS provided the most significant genetic findings. These results suggest that employing the questionnaire which included standard diagnostic criteria of RLS could improve the accuracy of the survey-based studies.

Grey matter alterations in restless legs syndrome: A coordinate‐based meta‐analysis

“…It has been well documented that RLS is a disorder with a strong genetic background; however, RLS is genetically heterogeneous with large phenotype variability (Akcimen et al., 2019; Allen et al., 2014; Dauvilliers & Winkelmann, 2013; Jimenez‐Jimenez et al., 2018; Schormair et al., 2017; Tilch et al., 2020; Trenkwalder et al., 2018). As noted in Table 1, of the 13 VBM datasets, three did not report the family history of patients with RLS.…”

Validation of breast cancer risk assessment tools on a French-Canadian population-based cohort

“…The highest breast cancer risk among genotyped women (higher age at first live birth and more relatives with breast cancer) could not be explained by the women preferentially genotyped, as they were selected for studies unrelated with breast cancers. [30][31][32] Even though these two subcohorts were similar, it would be useful to collect all genotype information for the entire cohort to validate the PRS results. Finally, regarding family history included in the IBIS model, we only had maternal and paternal history of breast cancer and maternal history of ovary cancer.…”

“…These participants were selected to be genotyped through various scientific projects unrelated to breast cancer. [30][31][32] SNP positions were based on build GRCh37/hg19. The detailed pipeline about quality control and imputation can be found at www.…”

Exploration of restless legs syndrome under the new concept: A review

“…PLMS is also common in patients without symptoms of RLS and is found in approximately 7.63% to 25% of the general population. [ 11 ] A common misconception about RLS is that it is synonymous with periodic limb movement disorder (Periodic Limb Movement Disorder, PLMD), so PLMD or occasionally isolated PLMS is often misdiagnosed as RLS. The diagnosis of PLMD is limited to patients without RLS, in whom periodic limb movements during sleep are the primary sleep disorders associated with symptoms of insomnia or sleep deprivation.…”

“…[ 18 , 19 ] The pathophysiological functions of these genomic loci are yet to be defined, but their main functions appear to be related to the neural development of the limb during the embryonic period. [ 11 ] However, variation at these genomic loci accounts for only a small fraction of genetic susceptibility to RLS.…”