Login / Signup

Genomic analysis identifies risk factors in restless legs syndrome.

Fulya AkcimenRuth ChiaSara Saez-AtienzarPaola RuffoMemoona RasheedJay P RossCalwing LiaoAnindita RayPatrick A DionSonja W ScholzGuy A RouleauBryan J Traynor
Published in: medRxiv : the preprint server for health sciences (2023)
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. Here, we present a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in three population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE). Genome-wide association analysis identified nine independent risk loci, of which eight had been previously reported, and one was a novel risk locus ( LMX1B , rs35196838, OR = 1.14, 95% CI = 1.09-1.19, p -value = 2.2 × 10 -9 ). A genome-wide, gene-based common variant analysis identified GLO1 as an additional risk gene ( p -value = 8.45 × 10 -7 ). 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 (r g = 0.40, se = 0.08, p -value = 5.4 × 10 -7 ), depression (r g = 0.35, se = 0.06, p -value = 2.17 × 10 -8 ), and intelligence (r g = -0.20, se = 0.06, p- value = 4.0 × 10 -4 ). Our study expands the understanding of the genetic architecture of RLS and highlights the contributions of common variants to this prevalent neurological disorder.
Keyphrases
  • genome wide
  • copy number
  • dna methylation
  • genome wide association
  • risk factors
  • depressive symptoms
  • case report
  • brain injury
  • genome wide analysis
  • transcription factor
  • subarachnoid hemorrhage