Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia.
Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia.
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DOI：
10.1038/s41467-018-05510-z
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发表时间：
2018-08-06
影响因子：
16.6
通讯作者：
Koellinger PD
中科院分区：
文献类型：
--
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
较高的教育程度（EA）与精神分裂症（SZ）负相关。然而，最近的研究发现EA和SZ之间存在正的遗传相关。我们使用EA和SZ（N = 443，581）的全基因组关联研究结果和具有深度表型SZ患者的重复队列（1169例对照; 1067例病例）来调查这种违反直觉的发现的可能原因。我们发现EA和SZ之间存在很强的遗传依赖性，这不能用偶然、连锁不平衡或选择性交配来解释。相反，几个基因似乎对EA和SZ具有多效性作用，但没有明确的标志一致性模式。使用EA作为代理表型，我们分离FOXO 6和SLITRK 1作为SZ的新候选基因。我们的研究结果表明，目前SZ诊断聚集在至少两个疾病亚型：一部分类似于高智力和双相情感障碍（BIP），而另一部分是一个认知障碍，是独立的BIP。文化程度与精神分裂症有负表型相关，但有正遗传相关。在这里，作者研究了这两个性状之间的遗传依赖性，发现多个基因对两者都有多效性影响，而没有系统的符号一致性模式。
Higher educational attainment (EA) is negatively associated with schizophrenia (SZ). However, recent studies found a positive genetic correlation between EA and SZ. We investigate possible causes of this counterintuitive finding using genome-wide association study results for EA and SZ (N = 443,581) and a replication cohort (1169 controls; 1067 cases) with deeply phenotyped SZ patients. We find strong genetic dependence between EA and SZ that cannot be explained by chance, linkage disequilibrium, or assortative mating. Instead, several genes seem to have pleiotropic effects on EA and SZ, but without a clear pattern of sign concordance. Using EA as a proxy phenotype, we isolate FOXO6 and SLITRK1 as novel candidate genes for SZ. Our results reveal that current SZ diagnoses aggregate over at least two disease subtypes: one part resembles high intelligence and bipolar disorder (BIP), while the other part is a cognitive disorder that is independent of BIP. Educational attainment and schizophrenia have a negative phenotypic relationship but show positive genetic correlation. Here, the authors study genetic dependence between the two traits and find that multiple genes have pleiotropic effects on both without a systematic pattern of sign concordance.
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影响因子：
6.6
作者：
Le Hellard, Stephanie;Wang, Yunpeng;Andreassen, Ole A.
通讯作者：
Andreassen, Ole A.
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ