Abstract:

BACKGROUND: As the development of genome-wide association study, the simultaneous genotyping of thousands of single nucleotide polymorphisms have made genetic epidemiology studies come into a new phase. Generally, identification of genetic variants associated with human diseases is based on single base changes in the DNA sequence, some of which lead to alterations in protein structure and function. Therefore, those non-synonymous single nucleotide polymorphisms occurring in coding regions and causing an amino acid substitution or insertion of a stop codon are likely to affect the function of the proteins accounting for susceptibility to complex disease for altering the encoded amino acid sequence.
OBJECTIVE: To combine incorporating predicted function scores of non-synonymous single nucleotide polymorphisms with variable threshold test to improve the identification accuracy of susceptibility genes associated with complex diseases.
METHODS: Firstly, for non-synonymous single nucleotide polymorphisms, we computed their scale invariant feature transform and Polyphen-2 scores. Then weighted variable threshold tests were performed for 35 selected genes. The comparison with general association analysis was also performed.
RESULTS AND CONCLUSION: The results showed that the test power of our method was higher than general association test, and the identification accuracy of susceptibility genes was improved.