Myocardial infarction (MI) is characterized by abrupt occlusion of coronary artery resulting in irreversible damage to cardiac muscle. This disease might result from the interactions of multiple genetic and environmental factors, none of which can cause disease solely by themselves. To reveal the genetic bases of MI, we performed a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers. We have identified functional SNPs within the lymphotoxin-alpha gene located on chromosome 6p21 conferred susceptibility to MI. This chapter describes a detailed protocol for performing a genome-wide association study as used in our MI study.