Genetic association of FMRP targets with psychiatric disorders.
Genetic association of FMRP targets with psychiatric disorders.
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DOI：
10.1038/s41380-020-00912-2
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发表时间：
2021-07
影响因子：
11
通讯作者：
Pocklington AJ
中科院分区：
文献类型：
--
作者：
Clifton NE;Rees E;Holmans PA;Pardiñas AF;Harwood JC;Di Florio A;Kirov G;Walters JTR;O'Donovan MC;Owen MJ;Hall J;Pocklington AJ
编码脆性X智力低下蛋白（FMRP）的mRNA靶标的基因因与精神疾病的遗传关联而富集。然而，许多FMRP靶点具有本身与精神疾病遗传相关的功能，包括突触传递和可塑性，因此尚不清楚遗传风险是否真正与FMRP结合相关，或者是否由另一种特征或功能注释更好地表征的基因采样介导。使用已发表的常见变异、罕见编码变异和拷贝数变异数据，我们研究了FMRP结合与精神分裂症、重性抑郁症和双相情感障碍的遗传关联之间的关系。来自多种组织类型研究的FMRP高置信度靶点富集了常见的精神分裂症风险等位基因，以及精神分裂症病例中罕见的功能丧失和从头非同义变异。同样，通过常见的变异，FMRP靶点与重性抑郁症相关，我们提出了与双相情感障碍相关的新证据。这些关系无法用其他已知与精神疾病相关的功能注释来解释，包括与突触结构和功能相关的功能注释。这项研究加强了FMRP靶向捕获与一系列精神疾病遗传相关的基因亚群的证据。
Genes encoding the mRNA targets of fragile X mental retardation protein (FMRP) are enriched for genetic association with psychiatric disorders. However, many FMRP targets possess functions that are themselves genetically associated with psychiatric disorders, including synaptic transmission and plasticity, making it unclear whether the genetic risk is truly related to binding by FMRP or is alternatively mediated by the sampling of genes better characterised by another trait or functional annotation. Using published common variant, rare coding variant and copy number variant data, we examined the relationship between FMRP binding and genetic association with schizophrenia, major depressive disorder and bipolar disorder. High-confidence targets of FMRP, derived from studies of multiple tissue types, were enriched for common schizophrenia risk alleles, as well as rare loss-of-function and de novo nonsynonymous variants in schizophrenia cases. Similarly, through common variation, FMRP targets were associated with major depressive disorder, and we present novel evidence of association with bipolar disorder. These relationships could not be explained by other functional annotations known to be associated with psychiatric disorders, including those related to synaptic structure and function. This study reinforces the evidence that targeting by FMRP captures a subpopulation of genes enriched for genetic association with a range of psychiatric disorders.
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DOI：
10.1016/j.tig.2017.07.008
发表时间：
2017-10
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Davis JK;Broadie K
通讯作者：
Broadie K
影响因子：
12.3
作者：
Doherty JL;Owen MJ
通讯作者：
Owen MJ
影响因子：
11
作者：
Clifton NE;Pocklington AJ;Scholz B;Rees E;Walters JT;Kirov G;O'Donovan MC;Owen MJ;Wilkinson LS;Thomas KL;Hall J
通讯作者：
Hall J
DOI：
10.1159/000506858
发表时间：
2020-10
期刊：
Complex psychiatry
影响因子：
--
作者：
Clifton NE;Thomas KL;Wilkinson LS;Hall J;Trent S
通讯作者：
Trent S
DOI：
10.1038/ejhg.2015.218
发表时间：
2016-06
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Ambalavanan A;Girard SL;Ahn K;Zhou S;Dionne-Laporte A;Spiegelman D;Bourassa CV;Gauthier J;Hamdan FF;Xiong L;Dion PA;Joober R;Rapoport J;Rouleau GA
通讯作者：
Rouleau GA