In recent years, there has been a significant academic drive to determine the cause of the missing heritability problem which is commonly associated with the genetics of complex traits such as complex diseases. In this paper, I present an in-depth literature review by introducing the nature of this problem and discussing the current state of genetic association studies which commonly involves multi-locus models as predictors (as opposed to the conventional single-locus association studies) that became prominent with the advent of genome-wide sequencing technology.