Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Eur J Hum Genet. 2019 Jun;27(6):963-969. doi: 10.1038/s41431-019-0349-x. Epub 2019 Feb 5.
Some of the most widely studied variants in psychiatric genetics include variable number tandem repeat variants (VNTRs) in SLC6A3, DRD4, SLC6A4, and MAOA. While initial findings suggested large effects, their importance with respect to psychiatric phenotypes is the subject of much debate with broadly conflicting results. Despite broad interest, these loci remain absent from the largest available samples, such as the UK Biobank, limiting researchers' ability to test these contentious hypotheses rigorously in large samples. Here, using two independent reference datasets, we report out-of-sample imputation accuracy estimates of >0.96 for all four VNTR variants and one modifying SNP, depending on the reference and target dataset. We describe the imputation procedures of these candidate variants in 486,551 UK Biobank individuals, and have made the imputed variant data available to UK Biobank researchers. This resource, provided to the scientific community, will allow the most rigorous tests to-date of the roles of these variants in behavioral and psychiatric phenotypes.
一些在精神遗传学中研究最广泛的变体包括 SLC6A3、DRD4、SLC6A4 和 MAOA 中的可变数目串联重复（VNTR）变体。虽然最初的发现表明了它们的重要性，但它们对精神表型的重要性是一个备受争议的话题，结果广泛存在冲突。尽管人们广泛关注这些基因座，但它们在最大的现有样本中（例如英国生物银行）仍然缺失，这限制了研究人员在大型样本中严格测试这些有争议的假设的能力。在这里，我们使用两个独立的参考数据集，报告了所有四个 VNTR 变体和一个修饰 SNP 的样本外估计精度>0.96，这取决于参考和目标数据集。我们描述了在 486,551 名英国生物银行个体中这些候选变体的导入程序，并向英国生物银行研究人员提供了导入的变体数据。该资源提供给科学界，将允许对这些变体在行为和精神表型中的作用进行迄今为止最严格的测试。
