Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common spinal disorder among the elderly that causes myelopathy and radiculopathy. To identify genetic factors for OPLL, we performed a genome-wide association study (GWAS) in ∼8,000 individuals followed by a replication study using an additional ∼7,000 individuals. We identified six susceptibility loci for OPLL: 20p12.3 (rs2423294: P = 1.10 × 10(-13)), 8q23.1 (rs374810: P = 1.88 × 10(-13)), 12p11.22 (rs1979679: P = 4.34 × 10(-12)), 12p12.2 (rs11045000: P = 2.95 × 10(-11)), 8q23.3 (rs13279799: P = 1.28 × 10(-10)) and 6p21.1 (rs927485: P = 9.40 × 10(-9)). Analyses of gene expression in and around the loci suggested that several genes are involved in OPLL etiology through membranous and/or endochondral ossification processes. Our results bring new insight to the etiology of OPLL.