APOA2, Dietary Fat, and Body Mass Index

Abstract

Genomics is revolutionizing biomedical research and providing great expectations with regard to disease prevention and treatment.¹ The classic candidate gene approach and the newer genome-wide association studies² have identified genetic variants that predispose patients to common diseases. If the current trends continue, most common disease-predisposition polymorphisms will soon be identified. Thus, a major remaining research challenge will be to characterize gene-environment interactions because these are essential for the translation of genomics into clinical medicine and improved public health.³ Diet is one of the most important environmental factors that interacts with the genome to modulate disease risk,⁴ and better understanding of these interactions has the potential to support disease prevention via modification of dietary recommendations. However, progress in this area has been slow because of the low evidence level achieved so far. Although studies^4-7 reported enticing gene-diet interactions, their level of replication has been extremely low. Thus, a vast proportion of gene-diet interactions has not been replicated. Only a small number of interactions have been replicated twice, and, to the best of our knowledge, none has been replicated in 3 or more independent populations. This problem has plagued classic genotype-phenotype association studies and, currently, consistency is thought to be a crucial causal criterion of credibility of genome-wide association studies.⁸ Therefore, the National Cancer Institute–National Human Genome Research Institute Working Group on Replication in Genotype-Phenotype Associations⁹ supports replication as the most reliable approach to increase evidence level and subsequent clinical applications.