Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark.
deCODE Genetics, 101, Reykjavik, Iceland.
Commun Biol. 2020 Nov 25;3(1):703. doi: 10.1038/s42003-020-01430-1.
Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10), rs10068599-T (OR = 1.09, P = 6.9 × 10) and rs10769894-A (OR = 0.90, P = 9.4 × 10). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.
不宁腿综合征（RLS）是一种常见的神经感觉运动障碍，常被描述为一种不愉快的感觉，伴有移动腿部的冲动。在这里，我们报告了一项对 RLS 的全基因组关联研究的荟萃分析结果，该研究包括 480982 名白种人（病例=10257）和 24977 名后续样本（病例=6651）。我们证实了之前在 19 个基因座报告的 20 个 RLS 序列变异中的 19 个，并报告了三个新的 RLS 关联；rs112716420-G（OR=1.25，P=1.5×10），rs10068599-T（OR=1.09，P=6.9×10）和 rs10769894-A（OR=0.90，P=9.4×10）。在 22 个 RLS 基因座中的四个基因座中，顺式-eQTL 分析表明对基因表达有因果影响。通过 RLS 的多基因风险评分，我们扩展了先前的流行病学发现，表明肥胖、吸烟和大量饮酒是 RLS 的危险因素。为了提高我们的认识，寻求更好的治疗方法，需要更多的遗传学研究，以深入了解疾病的生物学。
