Fulya Akçimen, Ruth Chia, Sara Saez-Atienzar, Paola Ruffo, Memoona Rasheed, Jay P. Ross, Calwing Liao, Anindita Ray, Patrick A. Dion, Sonja W. Scholz, Guy A. Rouleau, Bryan J. Traynor
{"title":"基因组分析确定不安腿综合征的风险因素","authors":"Fulya Akçimen, Ruth Chia, Sara Saez-Atienzar, Paola Ruffo, Memoona Rasheed, Jay P. Ross, Calwing Liao, Anindita Ray, Patrick A. Dion, Sonja W. Scholz, Guy A. Rouleau, Bryan J. Traynor","doi":"10.1002/ana.27040","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. We sought to identify additional novel genetic risk factors associated with RLS susceptibility.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We performed a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (<i>n</i> = 9,851) and controls (<i>n</i> = 38,957) in 3 population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Genome-wide association analysis identified 9 independent risk loci, of which 8 had been previously reported, and 1 was a novel risk locus (<i>LMX1B</i>, rs35196838, OR 1.14, 95% CI 1.09–1.19, <i>p</i> value = 2.2 × 10<sup>−9</sup>). Furthermore, a transcriptome-wide association study also identified <i>GLO1</i> and a previously unreported gene, <i>ELFN1</i>. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (<i>r</i><sub>g</sub> = 0.40, se = 0.08, <i>p</i> value = 5.4 × 10<sup>−7</sup>), depression (<i>r</i><sub>g</sub> = 0.35, se = 0.06, <i>p</i> value = 2.17 × 10<sup>−8</sup>), and intelligence (<i>r</i><sub>g</sub> = −0.20, se = 0.06, <i>p</i> value = 4.0 × 10<sup>−4</sup>).</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>Our study expands the understanding of the genetic architecture of RLS, and highlights the contributions of common variants to this prevalent neurological disorder. ANN NEUROL 2024;96:994–1005</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496024/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome\",\"authors\":\"Fulya Akçimen, Ruth Chia, Sara Saez-Atienzar, Paola Ruffo, Memoona Rasheed, Jay P. Ross, Calwing Liao, Anindita Ray, Patrick A. Dion, Sonja W. Scholz, Guy A. Rouleau, Bryan J. Traynor\",\"doi\":\"10.1002/ana.27040\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. We sought to identify additional novel genetic risk factors associated with RLS susceptibility.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We performed a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (<i>n</i> = 9,851) and controls (<i>n</i> = 38,957) in 3 population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Genome-wide association analysis identified 9 independent risk loci, of which 8 had been previously reported, and 1 was a novel risk locus (<i>LMX1B</i>, rs35196838, OR 1.14, 95% CI 1.09–1.19, <i>p</i> value = 2.2 × 10<sup>−9</sup>). Furthermore, a transcriptome-wide association study also identified <i>GLO1</i> and a previously unreported gene, <i>ELFN1</i>. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (<i>r</i><sub>g</sub> = 0.40, se = 0.08, <i>p</i> value = 5.4 × 10<sup>−7</sup>), depression (<i>r</i><sub>g</sub> = 0.35, se = 0.06, <i>p</i> value = 2.17 × 10<sup>−8</sup>), and intelligence (<i>r</i><sub>g</sub> = −0.20, se = 0.06, <i>p</i> value = 4.0 × 10<sup>−4</sup>).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>Our study expands the understanding of the genetic architecture of RLS, and highlights the contributions of common variants to this prevalent neurological disorder. ANN NEUROL 2024;96:994–1005</p>\\n </section>\\n </div>\",\"PeriodicalId\":127,\"journal\":{\"name\":\"Annals of Neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2024-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496024/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ana.27040\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ana.27040","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome
Objective
Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. We sought to identify additional novel genetic risk factors associated with RLS susceptibility.
Methods
We performed a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in 3 population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE).
Results
Genome-wide association analysis identified 9 independent risk loci, of which 8 had been previously reported, and 1 was a novel risk locus (LMX1B, rs35196838, OR 1.14, 95% CI 1.09–1.19, p value = 2.2 × 10−9). Furthermore, a transcriptome-wide association study also identified GLO1 and a previously unreported gene, ELFN1. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (rg = 0.40, se = 0.08, p value = 5.4 × 10−7), depression (rg = 0.35, se = 0.06, p value = 2.17 × 10−8), and intelligence (rg = −0.20, se = 0.06, p value = 4.0 × 10−4).
Interpretation
Our study expands the understanding of the genetic architecture of RLS, and highlights the contributions of common variants to this prevalent neurological disorder. ANN NEUROL 2024;96:994–1005
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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