Chapter 32 - Family and genome-wide association studies of restless legs syndrome

Summary

In order to better understand the different roles genetic factors can play in restless legs syndrome (RLS), it is important to recognize that RLS can be a primary disorder or secondary to a number of other medical conditions, such as iron deficiency, pregnancy, and renal failure. To date, three genome-wide association studies (GWAS) have been performed for RLS and one for RLS and periodic limb movements in sleep (PLMS). Both family and association studies have implicated candidate genomic regions and candidate genes in RLS. With respect to GWAS, genetic heterogeneity is exemplified by the fact that the currently identified association signals only account for approximately 6.8% of the projected heritability although they confer relatively large risk increases. RLS is a genetically complex disease and this complexity is probably not only marked by locus heterogeneity but also by the range of different variants likely to be involved.