Reimers Mark A, Craver Carl, Dozmorov Mikhail, Bacanu Silviu-Alin, Kendler Kenneth S
Neuroscience Program and Department of Biomedical Engineering, Michigan State University, 775 Woodlot Rd, East Lansing, MI, 48824, USA.
Philosophy-Neuroscience-Psychology Program, Washington University in St. Louis, St. Louis, USA.
Behav Genet. 2019 Mar;49(2):187-195. doi: 10.1007/s10519-018-9935-x. Epub 2018 Nov 16.
Genome wide association studies (GWAS) for behavioral traits and psychiatric disorders have inspired both confident optimism and withering criticism. Although many recent findings from well powered GWAS have been replicated in independent data sets, the genes identified have pinned down few if any underlying causal mechanisms. Therefore, a key issue is whether or not the genes implicated by GWAS form a coherent story on their own and thus could in principle lead to insight into the biological mechanisms underlying the trait or disorder. We sketch here four scenarios for how genes may contribute to traits and disorders; genetic studies may help elucidate mechanisms under only two of our scenarios. We also describe here an approach to characterize, in an unbiased fashion, the molecular coherence of the gene sets implicated by GWAS of various behavioral and psychiatric phenotypes and we sketch how the four scenarios may be reflected in our molecular coherence measure.
针对行为特征和精神疾病的全基因组关联研究（GWAS）既引发了坚定的乐观情绪，也招致了严厉的批评。尽管近期许多来自大规模GWAS的研究结果已在独立数据集中得到重复验证，但所鉴定出的基因几乎没有确定任何潜在的因果机制。因此，一个关键问题是，GWAS所涉及的基因自身能否构成一个连贯的故事，从而原则上能否有助于深入了解该特征或疾病背后的生物学机制。我们在此概述了基因可能导致特征和疾病的四种情形；基因研究可能仅在我们所描述的两种情形下有助于阐明机制。我们还在此描述了一种方法，以无偏倚的方式表征各种行为和精神疾病表型的GWAS所涉及的基因集的分子连贯性，并概述这四种情形如何在我们的分子连贯性测量中得到体现。
