BACKGROUND: Previous studies have not explored the relationship between a single gene and a single disease. Our study aims to investigate the association of multiple genotypes with blood lead levels and bone matrix density (BMD) by using genetic algorithms. METHODS: Our research focused on 506 employees (245 males and 261 females) of a lead battery factory in Taiwan. We collected data on their BMD, blood lead level, and 6 SNPs (ACE, alpha-adducin, Bsm, Tag, Apa, and ALAD); these factors were analyzed using discrete binary particle swarm optimization (DBPSO) and logistic regression analysis. RESULTS: We found no association between blood lead level and bone density, which may be due to the relatively young age of this population (mean age = 45.1 years). However, the genotype that contained both Bsm type bb and ALAD type 1-1 may play an important role in protecting against lower bone density among these employees. CONCLUSIONS: In conclusion, this study found that the Bsm and ALAD genes influence bone density among lead workers. However, the mechanism and exact relationship between these two genes and bone density require further investigation.