Analysis of Shared Heritability in Common Disorders of the Brain
Analysis of Shared Heritability in Common Disorders of the Brain
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DOI：
10.1101/048991
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
V. Anttila;B. Bulik-Sullivan;H. Finucane;J. Bras;L. Duncan;V. Escott-Price;Guido J Falcone;P. Gormley;R. Malik;N. Patsopoulos;S. Ripke;Raymond K. Walters;Zhi Wei;Dongmei Yu;Dongmei Yu;Phil H. Lee;Phil H. Lee;Metastroke;Ocd;G. Breen;C. M. Bulik;M. Daly;M. Dichgans;S. Faraone;Rita Guerreiro;P. Holmans;P. Holmans;K. Kendler;B. Koeleman;Carol A. Mathews;J. Scharf;P. Sklar;Julie Williams;N. Wood;C. Cotsapas;C. Cotsapas;A. Palotie;J. W. Smoller;P. Sullivan;J. Rosand;A. Corvin;B. Neale
中科院分区：
文献类型：
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作者：
V. Anttila;B. Bulik-Sullivan;H. Finucane;J. Bras;L. Duncan;V. Escott-Price;Guido J Falcone;P. Gormley;R. Malik;N. Patsopoulos;S. Ripke;Raymond K. Walters;Zhi Wei;Dongmei Yu;Dongmei Yu;Phil H. Lee;Phil H. Lee;Metastroke;Ocd;G. Breen;C. M. Bulik;M. Daly;M. Dichgans;S. Faraone;Rita Guerreiro;P. Holmans;P. Holmans;K. Kendler;B. Koeleman;Carol A. Mathews;J. Scharf;P. Sklar;Julie Williams;N. Wood;C. Cotsapas;C. Cotsapas;A. Palotie;J. W. Smoller;P. Sullivan;J. Rosand;A. Corvin;B. Neale
脑疾病表现出相当大的流行病学共病性，并经常共享症状，引发了关于其病因重叠程度的争论。我们基于对215，683名患者和657，164名对照的全基因组关联研究的汇总统计数据，量化了25种脑部疾病的遗传共享，以及它们与来自1，191，588名个体的17种表型的关系。精神疾病显示出共同变异风险的实质性共享，而神经系统疾病则显得彼此更加不同。我们观察到神经系统疾病和精神疾病之间共享的证据有限，但确实确定了疾病和几种认知测量之间的强大共享，以及疾病和人格类型。我们还进行了广泛的模拟，以探讨功率，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来源的重要性，以及基于遗传性的方法在理解其病因学方面的价值。
Disorders of the brain exhibit considerable epidemiological comorbidity and frequently share symptoms, provoking debate about the extent of their etiologic overlap. We quantified the genetic sharing of 25 brain disorders based on summary statistics from genome-wide association studies of 215,683 patients and 657,164 controls, and their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders show substantial sharing of common variant risk, while neurological disorders appear more distinct from one another. We observe limited evidence of sharing between neurological and psychiatric disorders, but do identify robust sharing between disorders and several cognitive measures, as well as disorders and personality types. We also performed extensive simulations to explore how power, diagnostic misclassification and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a source of risk for brain disorders and the value of heritability-based methods in understanding their etiology.