Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology.
Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology.
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DOI：
10.1038/s41467-022-34418-y
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发表时间：
2022-11-11
影响因子：
16.6
通讯作者：
Lencz, Todd
中科院分区：
文献类型：
--
作者：
Lam, Max;Chen, Chia-Yen;Hill, W. David;Xia, Charley;Tian, Ruoyu;Levey, Daniel F.;Gelernter, Joel;Stein, Murray B.;Hatoum, Alexander S.;Huang, Hailiang;Malhotra, Anil K.;Runz, Heiko;Ge, Tian;Lencz, Todd
已知认知缺陷与大多数形式的精神病理学有关。在这里，我们进行局部遗传相关性分析作为一种手段，以确定独立的基因组片段，显示生物学上可解释的多效性之间的关联认知维度和精神病理学。我们确定集体的基因组片段，我们称之为“元基因座”，表现出不同的多效性模式的精神病理学相对于认知任务的性能（CTP）或性能的非认知因素（NCF）来自教育程度。我们观察到，在产前早期儿童时期表达的神经发育基因集占主导地位的CTP相关的元基因座，而出生后的基因集更多地参与NCF相关的元基因座。此外，我们表明，神经发育基因集是解离跨CTP元基因座就其在整个大脑的空间分布。此外，我们发现，GABA能，胆碱能和β-amatergic基因驱动多效性的关系内分离的元基因座。认知障碍是精神病理学的一个关键特征。在这里，作者利用认知维度和精神病理学之间的遗传重叠来解析精神疾病的生物学，并确定以特定重叠模式为特征的“元基因座”基因组片段。
Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identify collective segments of the genome, which we call “meta-loci”, showing differential pleiotropic patterns for psychopathology relative to either cognitive task performance (CTP) or performance on a non-cognitive factor (NCF) derived from educational attainment. We observe that neurodevelopmental gene sets expressed during the prenatal-early childhood period predominate in CTP-relevant meta-loci, while post-natal gene sets are more involved in NCF-relevant meta-loci. Further, we demonstrate that neurodevelopmental gene sets are dissociable across CTP meta-loci with respect to their spatial distribution across the brain. Additionally, we find that GABA-ergic, cholinergic, and glutamatergic genes drive pleiotropic relationships within dissociable meta-loci. Cognitive impairments are a key feature of psychopathology. Here, authors exploit the genetic overlap between cognitive dimensions and psychopathology to parse the biology of psychiatric illness and identify “meta-loci” genome segments characterized by specific patterns of overlap.
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影响因子：
16.6
作者：
Bansal V;Mitjans M;Burik CAP;Linnér RK;Okbay A;Rietveld CA;Begemann M;Bonn S;Ripke S;de Vlaming R;Nivard MG;Ehrenreich H;Koellinger PD
通讯作者：
Koellinger PD
影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
30.8
作者：
Grotzinger, Andrew D.;Mallard, Travis T.;Akingbuwa, Wonuola A.;Ip, Hill F.;Adams, Mark J.;Lewis, Cathryn M.;McIntosh, Andrew M.;Grove, Jakob;Dalsgaard, Soren;Lesch, Klaus-Peter;Strom, Nora;Meier, Sandra M.;Mattheisen, Manuel;Borglum, Anders D.;Mors, Ole;Breen, Gerome;Lee, Phil H.;Kendler, Kenneth S.;Smoller, Jordan W.;Tucker-Drob, Elliot M.;Nivard, Michel G.
通讯作者：
Nivard, Michel G.
影响因子：
5.3
作者：
Green, Michael F.
通讯作者：
Green, Michael F.