Genome-wide association study for mandibular prognathism using microsatellite and pooled DNA method.

INTRODUCTION: The purpose of this study was to extend an association study from chromosome 1 to the whole genome (genome-wide association study) to find susceptibility loci of mandibular prognathism. METHODS: Two hundred forty patients diagnosed with mandibular prognathism and 360 healthy controls of Japanese descent were recruited. The typing of microsatellites covering the whole genome was conducted using a pooled DNA method. Upon completion of the first and second screenings with pooled DNA, the positive microsatellite markers from both the first and second typings were retyped using individual-subject DNA samples to confirm the significance of allele frequency. RESULTS: Six microsatellites (D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i) showed differences between allele frequencies of the subjects and controls at P <0.001. D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i were located on chromosomes 1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22, respectively. SSX2IP, PLXNA2, RASA2, TCF21, CALN1, and RORA were suggested as candidate genes. CONCLUSIONS: The genome-wide association study using microsatellites suggested that 6 loci (1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22) were susceptibility regions of mandibular prognathism. The locus 1p22.3 was supported by a previous linkage analysis, and the other 5 were novel loci.