Analytic Translational Genetics Unit, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Science. 2018 Jun 22;360(6395). doi: 10.1126/science.aap8757.
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
脑部疾病在流行病学上具有相当大的共病性，且常具有相似的症状，这引发了关于它们病因重叠的争论。我们从 265218 名患者和 784643 名对照参与者的全基因组关联研究中，对 25 种脑部疾病的遗传共享进行了量化，并评估了它们与 17 种表型的关系，这些表型来自于 1191588 个人。精神疾病具有共同的变异风险，而神经疾病彼此之间以及与精神疾病相比，表现出更为明显的差异。我们还发现了疾病与许多脑表型之间存在显著的共享，包括认知测量。此外，我们进行了模拟，以探讨统计能力、诊断错误分类和表型异质性如何影响遗传相关性。这些结果强调了常见遗传变异作为脑部疾病风险因素的重要性，以及基于遗传率的方法在理解其病因学方面的价值。
