The impact of educational attainment, intelligence and intellectual disability on schizophrenia: a Swedish population-based register and genetic study.

The impact of educational attainment, intelligence and intellectual disability on schizophrenia: a Swedish population-based register and genetic study.
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DOI:
10.1038/s41380-022-01500-2
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发表时间:
2022-05
影响因子:
11
通讯作者:
Sullivan, Patrick F.
Sullivan, Patrick F.
中科院分区:
医学1区
文献类型:
--
作者:
Song, Jie;Yao, Shuyang;Kowalec, Kaarina;Lu, Yi;Sariaslan, Amir;Szatkiewicz, Jin P.;Larsson, Henrik;Lichtenstein, Paul;Hultman, Christina M.;Sullivan, Patrick F.

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精神分裂症(SCZ)是高度异质性的,没有亚型的治疗反应或纵向过程。认知功能障碍是SCZ的核心临床特征,也是预后较差的决定因素。SCZ和认知特征之间的遗传重叠是复杂的,全面的流行病学和基因组证据的研究有限。为了研究SCZ与三种认知特征(教育程度(EDU)、病前认知能力和智力残疾(ID))之间的关系,我们使用了两个瑞典样本:一个国家队列(14,230例SCZ病例和3,816,264例对照)和一个具有全面遗传数据的子样本(4992例病例和6009例对照)。以人群为基础的分析证实了认知能力差是SCZ的一个危险因素,家系和基于SNP的遗传相关性是可比的。在基因分型的病例中,那些具有高EDU和病前认知能力的人往往具有更高的EDU和智力的多基因风险评分(PRS)和更少的罕见外显子变异。最后,通过应用经验聚类方法,我们将SCZ病例分为四个可复制的亚组,其特征在于EDU和ID。特别是,在全国队列中EDU较高的亚组具有较少的不良结局,包括长期住院和死亡。在基因分型的子样本中,该亚组的EDU PRS较高,且与对照组相比,没有多余的罕见遗传负担。总之,我们发现了广泛的证据,认知特征和SCZ之间的强大关系,强调了认知在解剖SCZ的异质性的重要性。
Schizophrenia (SCZ) is highly heterogenous and no subtypes characterizing treatment response or longitudinal course well. Cognitive impairment is a core clinical feature of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive traits is complex, with limited studies of comprehensive epidemiological and genomic evidence. To examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two Swedish samples: a national cohort (14,230 SCZ cases and 3,816,264 controls) and a subsample with comprehensive genetic data (4992 cases and 6009 controls). Population-based analyses confirmed worse cognition as a risk factor for SCZ, and the pedigree and SNP-based genetic correlations were comparable. In the genotyped cases, those with high EDU and premorbid cognitive ability tended to have higher polygenetic risk scores (PRS) of EDU and intelligence and fewer rare exonic variants. Finally, by applying an empirical clustering method, we dissected SCZ cases into four replicable subgroups characterized by EDU and ID. In particular, the subgroup with higher EDU in the national cohort had fewer adverse outcomes including long hospitalization and death. In the genotyped subsample, this subgroup had higher PRS of EDU and no excess of rare genetic burdens than controls. In conclusion, we found extensive evidence of a robust relation between cognitive traits and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.
DOI: 10.1038/s41467-018-05510-z
发表时间: 2018-08-06
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
基因发现和多基因预测,从基因组全基因组协会的教育程度研究中,有110万个人。
DOI: 10.1038/s41588-018-0147-3
发表时间: 2018-07-23
期刊: Nature genetics
影响因子: 30.8
作者:
Lee JJ;Wedow R;Okbay A;Kong E;Maghzian O;Zacher M;Nguyen-Viet TA;Bowers P;Sidorenko J;Karlsson Linnér R;Fontana MA;Kundu T;Lee C;Li H;Li R;Royer R;Timshel PN;Walters RK;Willoughby EA;Yengo L;23andMe Research Team;COGENT (Cognitive Genomics Consortium);Social Science Genetic Association Consortium;Alver M;Bao Y;Clark DW;Day FR;Furlotte NA;Joshi PK;Kemper KE;Kleinman A;Langenberg C;Mägi R;Trampush JW;Verma SS;Wu Y;Lam M;Zhao JH;Zheng Z;Boardman JD;Campbell H;Freese J;Harris KM;Hayward C;Herd P;Kumari M;Lencz T;Luan J;Malhotra AK;Metspalu A;Milani L;Ong KK;Perry JRB;Porteous DJ;Ritchie MD;Smart MC;Smith BH;Tung JY;Wareham NJ;Wilson JF;Beauchamp JP;Conley DC;Esko T;Lehrer SF;Magnusson PKE;Oskarsson S;Pers TH;Robinson MR;Thom K;Watson C;Chabris CF;Meyer MN;Laibson DI;Yang J;Johannesson M;Koellinger PD;Turley P;Visscher PM;Benjamin DJ;Cesarini D
通讯作者: Cesarini D
DOI: 10.1038/ng.3211
发表时间: 2015-03
期刊: NATURE GENETICS
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.
DOI: 10.1038/nature18642
发表时间: 2016-08-04
期刊: NATURE
影响因子: 64.8
作者:
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DOI: 10.1093/schbul/sbw085
发表时间: 2017-05-01
影响因子: 6.6
作者:
Le Hellard, Stephanie;Wang, Yunpeng;Andreassen, Ole A.
通讯作者: Andreassen, Ole A.