Frequent traffic accidents constitute a major danger to human beings. The accident-prone driver who has the stable physiological, psychological, and behavioral characteristics is one of the most prominent causes of traffic accidents. The internal link between the individual characteristics and the accident proneness has been a difficult point in the accident prevention research. The authors selected accident-prone drivers as cases and safe drivers as controls (case-control group) from 18,360 drivers who were enrolled from three public transportation incorporations of China using area stratified sampling method. The case-control groups were 1:1 matched. The authors performed genome-wide association study (GWAS) by 179 cases and 179 controls using the U.S. Affymetrix Genome-Wide Human Mapping SNP 6.0 Array. The authors observed that the gene frequencies of 34 single-nucleotide polymorphisms (SNPs) in three regions of cases were higher than those in the control ( <10 ). The authors then tested two independent replication sets for strong association 6 SNPs in 349 pairs of case-control drivers using the U.S. ABI 3730 sequencing method. The results indicated that SNP rs6069499 within linked CBLN4 gene are strongly associated with accident proneness ( =6.37×10 ). According to CBLN4 gene mainly involved in adrenal development and the regulation of secretion, the authors performed 12 biochemical parameters of the blood using radioimmunoassay. The levels of dopamine (DA) and adrenocorticotropic (ACTH) hormone showed significant differences between accident-prone drivers and safe drivers ( =0.03, =0.01). It is suggested that the accident-prone drivers may have the idiosyncrasy of susceptibility.