Rs3923809

This SNP, located in an intron of the BTBD9 gene, has a variant that is seen somewhat more frequently in individuals with restless legs syndrome. The risk allele is rs3923809(A); carriers of two such alleles, i.e. those with rs3923809(A;A) genotypes, are estimated to be 1.9 fold more likely to have restless legs syndrome than rs3923809(G;G) individuals. The authors of this study suggest that perhaps half of the cases of restless legs syndrome may involve the rs3923809 risk genotypes.

Consistent with this finding, another report about rs3923809 links the (G) minor allele to a lower frequency of restless legs syndrome with an overall odds ratio of 0.57 (CI: 0.48-0.68).

Note that 70-80% of all individuals in European populations carry one or two copies of the (A) major allele, yet restless legs syndrome is thought to affect less than 10% of all adults. Therefore, although an individual may be at higher risk based on their genotype, the genotype by itself certainly isn't able to predictably cause restless legs syndrome.

The association between rs3923809 and RLS has been replicated in three European populations, and shows the most consistent effect across populations of several SNPs studied.

The results of a 2013 study of Korean patients suggest that the role of BTBD9 in the pathogenesis of restless legs syndrome is more universal across populations than previously reported and more efforts should be focused on the role of epistasis in the genetic architecture of restless legs syndrome. A significant association was found for rs3923809 and rs9296249 in BTBD9.

Association of restless legs syndrome variants in Korean patients with restless legs syndrome.