HS-MMGKG: A Fast Multi-objective Harmony Search Algorithm for Two-locus Model Detection in GWAS

Background:: Genome-Wide Association Study (GWAS) plays a very important role in identifying the causes of a disease. Because most of the existing methods for genetic-interaction detection in GWAS are designed for a single-correlation model, their performances vary considerably for different disease models. These methods usually have high computation cost and low accuracy. Method:: We present a new multi-objective heuristic optimization methodology named HSMMGKG for detecting genetic interactions. In HS-MMGKG, we use harmony search with five objective functions to improve the efficiency and accuracy. A new strategy based on p-value and MDR is adopted to generate more reasonable results. The Boolean representation in BOOST is modified to calculate the five functions rapidly. These strategies take less time complexity and have higher accuracy while detecting the potential models. Results:: We compared HS-MMGKG with CSE, MACOED and FHSA-SED using 26 simulated datasets. The experimental results demonstrate that our method outperforms others in accuracy and computation time. Our method has identified many two-locus SNP combinations that are associated with seven diseases in WTCCC dataset. Some of the SNPs have direct evidence in CTD database. The results may be helpful to further explain the pathogenesis. Conclusion:: It is anticipated that our proposed algorithm could be used in GWAS which is helpful in understanding disease mechanism, diagnosis and prognosis.