Genetic architecture of lumbar spinal stenosis

Introductory paragraph Over 100 million people worldwide suffer from lumbar spinal stenosis (LSS) with increasing incidence with ageing population, yet little is known about the LSS genetic background. Given the high cost of treating LSS, a deeper understanding of LSS pathogenesis may eventually result in the development of novel preventative and treatment methods, potentially leading to reductions in related societal costs. Our aim is to gain a better understanding of the genetic components underlying LSS. In the FinnGen, Estonian, and UK biobanks, we conduct a genome-wide association study (GWAS) of LSS and merge the results in the genome-wide meta-analysis. In addition to the seven known risk loci, our meta-analysis reveals 47 loci that have not been associated with LSS in previous studies. Many downstream analyses and multiple candidate genes discovered from the LSS-associated loci suggest that spinal degeneration plays a major role in the pathogenesis of LSS.