The “Golden Age” of Behavior Genetics?

Abstract

The search for genetic risk factors underlying the presumed heritability of all human behavior has unfolded in two phases. The first phase, characterized by candidate-gene-association (CGA) studies, has fallen out of favor in the behavior-genetics community, so much so that it has been referred to as a “cautionary tale.” The second and current iteration is characterized by genome-wide association studies (GWASs), single-nucleotide polymorphism (SNP) heritability estimates, and polygenic risk scores. This research is guided by the resurrection of, or reemphasis on, Fisher’s “infinite infinitesimal allele” model of the heritability of complex phenotypes, first proposed over 100 years ago. Despite seemingly significant differences between the two iterations, they are united in viewing the discovery of risk alleles underlying heritability as a matter of finding differences in allele frequencies. Many of the infirmities that beset CGA studies persist in the era of GWASs, accompanied by a host of new difficulties due to the human genome’s underlying complexities and the limitations of Fisher’s model in the postgenomics era.