Pleiotropy and Cross-Disorder Genetics Among Psychiatric Disorders.
Pleiotropy and Cross-Disorder Genetics Among Psychiatric Disorders.
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DOI：
10.1016/j.biopsych.2020.09.026
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发表时间：
2021-01-01
影响因子：
10.6
通讯作者：
Smoller JW
中科院分区：
文献类型：
--
作者：
Lee PH;Feng YA;Smoller JW
对常见和罕见遗传变异的全基因组分析记录了主要精神疾病的遗传性，建立了高度多基因遗传结构，并确定了数百种贡献变异。近年来，这些研究阐明了精神疾病遗传基础的另一个关键特征：多效性的重要作用和普遍性。现在很清楚，遗传对精神病理学的影响有很大一部分超越了临床诊断的界限。在这篇综述中，我们总结了在精神病学多效性的证据在多个层次的分析：从整体基因组范围内的相关性的生物学途径，并下降到单个基因座的水平。我们研究所观察到的多效性的潜在机制，包括神经发育的遗传效应，调控元件的不同作用，介导的影响，以及基因组变异与多种表型的虚假关联。最后，我们探讨了多效性对理解精神疾病的遗传基础，为疾病分类学提供信息，并推进精确精神病学和基因组医学的目标的影响。
Genome-wide analyses of common and rare genetic variation have documented the heritability of major psychiatric disorders, established their highly polygenic genetic architecture, and identified hundreds of contributing variants. In recent years, these studies have illuminated another key feature of the genetic basis of psychiatric disorders: the important role and pervasive nature of pleiotropy. It is now clear that a substantial fraction of genetic influences on psychopathology transcend clinical diagnostic boundaries. In this review, we summarize evidence in psychiatry for pleiotropy at multiple levels of analysis: from overall genome-wide correlation to biological pathways and down to the level of individual loci. We examine underlying mechanisms of observed pleiotropy including genetic effects on neurodevelopment, diverse actions of regulatory elements, mediated effects, and spurious associations of genomic variation with multiple phenotypes. We conclude with an exploration of the implications of pleiotropy for understanding the genetic basis of psychiatric disorders, informing nosology, and advancing the aims of precision psychiatry and genomic medicine.
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影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
DOI：
10.1002/ajmg.b.31063
发表时间：
2010-06-05
影响因子：
2.8
作者：
Ching, Michael S. L.;Shen, Yiping;Tan, Wen-Hann;Jeste, Shafali S.;Morrow, Eric M.;Chen, Xiaoli;Mukaddes, Nahit M.;Yoo, Seung-Yun;Hanson, Ellen;Hundley, Rachel;Austin, Christina;Becker, Ronald E.;Berry, Gerard T.;Driscoll, Katherine;Engle, Elizabeth C.;Friedman, Sandra;Gusella, James F.;Hisama, Fuki M.;Irons, Mira B.;Lafiosca, Tina;LeClair, Elaine;Miller, David T.;Neessen, Michael;Picker, Jonathan D.;Rappaport, Leonard;Rooney, Cynthia M.;Sarco, Dean P.;Stoler, Joan M.;Walsh, Christopher A.;Wolff, Robert R.;Zhang, Ting;Nasir, Ramzi H.;Wu, Bai-Lin
通讯作者：
Wu, Bai-Lin
DOI：
10.1146/annurev-genom-090314-024956
发表时间：
2016-08-31
影响因子：
8.7
作者：
Denny JC;Bastarache L;Roden DM
通讯作者：
Roden DM
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen