Phenotypic Annotation: Using Polygenic Scores to Translate Discoveries From Genome-Wide Association Studies From the Top Down
Phenotypic Annotation: Using Polygenic Scores to Translate Discoveries From Genome-Wide Association Studies From the Top Down
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DOI：
10.1177/0963721418807729
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发表时间：
2019-02-01
影响因子：
7.2
通讯作者：
Harden, K. Paige
中科院分区：
文献类型：
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作者：
Belsky, Daniel W.;Harden, K. Paige
全基因组关联研究（GWAS）已经确定了与复杂的人类特征和行为相关的特定遗传变异，如教育程度，精神障碍和人格。然而，个体变异的小效应量，发现的基因型生物学功能的不确定性，以及潜在的“皮肤外”环境机制，在GWAS结果和科学理解之间留下了一个翻译鸿沟，这将改善人类健康和福祉。我们提出了一套社会，行为和脑科学研究活动，映射发现的基因型神经，发育和社会机制，并呼吁这种研究计划表型注释。表型注释包括（a）详细阐述围绕已发现基因型的法则网络，（B）将关注点从单个基因转移到整个基因组，以及（c）测试已发现基因型如何影响寿命发育。表型注释研究已经推进了对GWAS在教育程度和精神分裂症方面的发现的理解。我们回顾的例子，并讨论心理学家采取的表型注释方法的方法论考虑。
Genome-wide association studies (GWASs) have identified specific genetic variants associated with complex human traits and behaviors, such as educational attainment, mental disorders, and personality. However, small effect sizes for individual variants, uncertainty regarding the biological function of discovered genotypes, and potential "outside-the-skin" environmental mechanisms leave a translational gulf between GWAS results and scientific understanding that will improve human health and well-being. We propose a set of social, behavioral, and brain-science research activities that map discovered genotypes to neural, developmental, and social mechanisms and call this research program phenotypic annotation. Phenotypic annotation involves (a) elaborating the nomological network surrounding discovered genotypes, (b) shifting focus from individual genes to whole genomes, and (c) testing how discovered genotypes affect life-span development. Phenotypic-annotation research is already advancing the understanding of GWAS discoveries for educational attainment and schizophrenia. We review examples and discuss methodological considerations for psychologists taking up the phenotypic-annotation approach.