Center for Quantitative Health, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Center for Quantitative Health, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Neurobiol Aging. 2018 Aug;68:160.e9-160.e14. doi: 10.1016/j.neurobiolaging.2018.03.008. Epub 2018 Mar 10.
We aimed to identify common genetic variations associated with delirium through genome-wide association testing in a hospital biobank. We applied a published electronic health record-based definition of delirium to identify cases of delirium, and control individuals with no history of delirium, from a biobank spanning 2 Boston academic medical centers. Among 6035 individuals of northern European ancestry, including 421 with a history of delirium, we used logistic regression to examine genome-wide association. We identified one locus spanning multiple genes, including 3 interleukin-related genes, associated with p = 1.41e-8, and 5 other independent loci with p < 5e-7. Our results do not support previously reported candidate gene associations in delirium. Identifying common-variant associations with delirium may provide insight into the mechanisms responsible for this complex and multifactorial outcome. Using standardized claims-based phenotypes in biobanks should allow the larger scale investigations required to confirm novel loci such as the one we identify.
我们旨在通过在医院生物库中进行全基因组关联测试来确定与谵妄相关的常见遗传变异。我们应用了已发表的基于电子健康记录的谵妄定义，从跨越 2 个波士顿学术医疗中心的生物库中确定了有谵妄病史的病例和没有谵妄病史的对照个体。在包括 421 名有谵妄病史的 6035 名北欧血统个体中，我们使用逻辑回归检查了全基因组关联。我们确定了一个跨越多个基因的基因座，包括与 p = 1.41e-8 相关的 3 个白细胞介素相关基因，以及其他 5 个独立的与 p < 5e-7 相关的基因座。我们的结果不支持以前在谵妄中报告的候选基因关联。确定与谵妄相关的常见变异关联可能有助于深入了解导致这种复杂和多因素结果的机制。在生物库中使用标准化的基于索赔的表型应该允许进行更大规模的研究，以确认我们所确定的新基因座等新基因座。
