Candidate Gene and Genome-Wide Association Studies in Behavioral Medicine

Abstract

In contrast with rare Mendelian (single-gene) diseases, the success rate of identification of genes for complex traits and diseases through positional cloning (i.e., fine-mapping of linkage peaks) has been disappointingly low. As a consequence, gene finding efforts for complex traits have increasingly come to rely on association approaches. The conduct of association studies has been greatly facilitated by the sequencing of the human genome in combination with major discovery efforts of single nucleotide polymorphisms (SNPs) such as the International HapMap Project. The increased availability of SNPs has spawned the development of two new association approaches: (1) candidate gene studies increasingly consider all common variants within the gene jointly, the so-called indirect association approach and (2) the genome-wide association (GWA) study. Especially the latter has led to an explosion in the number of newly identified genes for complex traits and diseases. These recent developments in genetic association studies have also impacted the field of behavioral medicine. Therefore, the current chapter provides an overview of concepts and approaches used in candidate gene and GWA studies illustrated with examples of traits and genes relevant to behavioral medicine.