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.

寻找所有人类行为的假定遗传性的遗传风险因素已经分两个阶段展开。以候选基因关联 (CGA) 研究为特征的第一阶段在行为遗传学界已经失宠，以至于它被称为“警示故事”。第二次和当前迭代的特点是全基因组关联研究 (GWAS)、单核苷酸多态性 (SNP) 遗传力估计和多基因风险评分。这项研究的指导是对 100 多年前首次提出的复杂表型遗传力的 Fisher 的“无限无穷小等位基因”模型的复活或重新强调。尽管两次迭代之间似乎存在显着差异，他们一致认为发现潜在遗传性的风险等位基因是发现等位基因频率差异的问题。困扰 CGA 研究的许多缺陷在 GWAS 时代仍然存在，同时由于人类基因组的潜在复杂性和后基因组时代 Fisher 模型的局限性，伴随着许多新的困难。