Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders.
Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders.
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DOI：
10.1038/s41398-021-01771-3
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发表时间：
2022-01-10
影响因子：
6.8
通讯作者：
Cormand B
中科院分区：
文献类型：
--
作者：
Cabana-Domínguez J;Torrico B;Reif A;Fernàndez-Castillo N;Cormand B
精神疾病非常普遍，并显示出相当大的临床和遗传重叠。多巴胺能和多巴胺能神经传递已被证明在许多精神疾病中发挥重要作用。在这里，我们的目标是评估这些系统的遗传贡献，八种精神疾病（注意力缺陷多动障碍（ADHD）、神经性厌食症（ANO）、自闭症谱系障碍（ASD）、双相情感障碍（BIP）、重度抑郁症（MD）、强迫症（OCD）、精神分裂症（SCZ）和抽动秽语综合征（TS））使用由精神病基因组学联盟进行的公开可用的GWAS分析，包括超过160，000例病例和275，000例对照。为此，我们详细阐述了四个不同的基因集：使用基因本体和KEGG途径工具对多巴胺（DA）和血清素（SERT）进行两个“宽”选择，以及手动策划的相同系统的两个“核心”选择。在基因水平上，我们发现67个来自DA和/或SERT基因组的基因与所研究的疾病之一显著相关，其中12个与两种不同的疾病相关。基因集分析显示，ADHD和ASD与广泛的DA基因集，BIP与广泛的SERT基因集，MD与核心SERT基因集有显着关联。有趣的是，对八种精神疾病的交叉疾病GWAS荟萃分析的询问显示与广泛的DA基因集相关。据我们所知，这是第一次系统地检查编码蛋白质的基因，这些蛋白质对这两种神经递质系统在这些疾病中的功能至关重要。我们的研究结果支持在几种精神疾病的多巴胺能和多巴胺能系统的多效性的贡献。
Psychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to play an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), anorexia nervosa (ANO), autism spectrum disorder (ASD), bipolar disorder (BIP), major depression (MD), obsessive-compulsive disorder (OCD), schizophrenia (SCZ) and Tourette’s syndrome (TS)) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium that include more than 160,000 cases and 275,000 controls. To do so, we elaborated four different gene sets: two ‘wide’ selections for dopamine (DA) and for serotonin (SERT) using the Gene Ontology and KEGG pathways tools, and two’core’ selections for the same systems, manually curated. At the gene level, we found 67 genes from the DA and/or SERT gene sets significantly associated with one of the studied disorders, and 12 of them were associated with two different disorders. Gene-set analysis revealed significant associations for ADHD and ASD with the wide DA gene set, for BIP with the wide SERT gene set, and for MD with the core SERT set. Interestingly, interrogation of a cross-disorder GWAS meta-analysis of the eight psychiatric conditions displayed association with the wide DA gene set. To our knowledge, this is the first systematic examination of genes encoding proteins essential to the function of these two neurotransmitter systems in these disorders. Our results support a pleiotropic contribution of the dopaminergic and serotonergic systems in several psychiatric conditions.
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影响因子：
11
作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
通讯作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
注意力缺陷多动障碍的遗传学。
影响因子：
11
作者：
Faraone SV;Larsson H
通讯作者：
Larsson H
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
DOI：
10.1016/s0140-6736(17)32802-7
发表时间：
2018-04-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
Cipriani A;Furukawa TA;Salanti G;Chaimani A;Atkinson LZ;Ogawa Y;Leucht S;Ruhe HG;Turner EH;Higgins JPT;Egger M;Takeshima N;Hayasaka Y;Imai H;Shinohara K;Tajika A;Ioannidis JPA;Geddes JR
通讯作者：
Geddes JR
DOI：
10.1176/appi.ajp.2017.16121402
发表时间：
2017-09-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Duncan L;Yilmaz Z;Gaspar H;Walters R;Goldstein J;Anttila V;Bulik-Sullivan B;Ripke S;Eating Disorders Working Group of the Psychiatric Genomics Consortium;Thornton L;Hinney A;Daly M;Sullivan PF;Zeggini E;Breen G;Bulik CM
通讯作者：
Bulik CM