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

Area of Science:

• Genetics
• Human Genomics
• Medical Genetics

Background:

• Mandibular prognathism is a skeletal malocclusion with a significant genetic component.
• Previous studies have identified some susceptibility loci, but a comprehensive genome-wide analysis was needed.

Purpose of the Study:

• To conduct a genome-wide association study (GWAS) to identify novel genetic loci associated with mandibular prognathism.
• To extend previous association studies from specific chromosomes to a whole-genome approach.

Main Methods:

• Recruited 240 patients with mandibular prognathism and 360 healthy controls of Japanese descent.
• Utilized whole-genome microsatellite typing with a pooled DNA method for initial screening.
• Confirmed significant findings by retyping positive markers using individual DNA samples.

Main Results:

• Identified six microsatellite loci (D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, D15S0154i) with significant allele frequency differences (P < 0.001).
• These loci are located at chromosomal positions 1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22.
• Suggested candidate genes including SSX2IP, PLXNA2, RASA2, TCF21, CALN1, and RORA.

Conclusions:

• The GWAS identified six susceptibility regions for mandibular prognathism at 1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22.
• The locus at 1p22.3 was consistent with prior linkage analysis findings.
• Five novel loci were identified, expanding the understanding of the genetic architecture of mandibular prognathism.