Association studies of variants in MEIS1, BTBD9, and MAP2K5/SKOR1 with restless legs syndrome in a US population

Background: A genome-wide association study (GWAS) identified significant association between variants in MEIS1, BTBD9, and MAP2K5/. SKOR1 and restless legs syndrome (RLS). However, many independent replication studies are needed to unequivocally establish a valid genotype-phenotype association across various populations. To further validate the GWAS findings, we investigated three variants, rs2300478 in MEIS1, rs9357271 in BTBD9, and rs1026732 in MAP2K5/. SKOR1 in 38 RLS families and 189 RLS patients/560 controls from the US for their association with RLS. Method: Both family-based and population-based case-control association studies were carried out. Results: The family-based study showed that SNP rs1026732 in MAP2K5/. SKOR1 was significantly associated with RLS (P= 0.01). Case-control association studies showed significant association between all three variants and RLS (P= 0.0001/OR = 1.65, P= 0.0021/OR = 1.59, and P= 0.0011/OR = 1.55 for rs2300478, rs9357271, and rs1026732, respectively). Conclusion: Variants in MEIS1, BTBD9, and MAP2K5/. SKOR1 confer a significant risk of RLS in a US population.