Family-based analysis of the contribution of rare and common genetic variants to school performance in schizophrenia.
Family-based analysis of the contribution of rare and common genetic variants to school performance in schizophrenia.
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DOI：
10.1038/s41380-023-02013-2
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发表时间：
2023-05
影响因子：
11
通讯作者：
Rees, Elliott
中科院分区：
文献类型：
--
作者：
Rammos, Alexandros;Kirov, George;Hubbard, Leon;Walters, James T. R.;Holmans, Peter;Owen, Michael J.;O'Donovan, Michael C.;Rees, Elliott
精神分裂症患者认知障碍与较差的功能预后相关。虽然已知遗传因素会导致精神分裂症患者的认知变化，但已经确定的具有强烈影响的罕见编码变异很少，而且新生、遗传和非遗传等位基因的相对影响尚不清楚。我们使用来自656对先证者父母三人组的阵列和外显子组测序数据来检查常见和罕见变异对精神分裂症患者学习表现的贡献，并由此暗示认知功能。父母遗传的常见等位基因有助于提高受教育程度（p值= 0.00015;OR = 2.63）和智力（p值= 0.00009;OR = 2.80），但与精神分裂症无关，与先证者的学习成绩较高相关。未传播的亲本共有等位基因未见显著影响。学习成绩较低的先证者在发育障碍（DD）相关基因中具有破坏性的新生编码变异（p值= 0.00026;OR = 11.6）。从父母遗传或非遗传的DD基因中极罕见的破坏性编码变异对学校表现没有影响。在学习成绩较差的先证者中，DD基因新生编码变异具有破坏性的先证者共病轻度智力障碍的发生率较高（p值= 0.0002;OR = 15.6）。总的来说，我们为精神分裂症的学校表现提供了罕见和常见的遗传贡献的证据。对DD基因中破坏性的新生编码变异的强烈影响提供了进一步的证据，证明精神分裂症中的认知障碍与发育障碍具有共同的病因。此外，在本样本中，我们报告没有证据表明非遗传的父母共同的认知特征等位基因通过对环境的间接影响来影响精神分裂症患者的学习表现。
Impaired cognition in schizophrenia is associated with worse functional outcomes. While genetic factors are known to contribute to variation in cognition in schizophrenia, few rare coding variants with strong effects have been identified, and the relative effects from de novo, inherited and non-transmitted alleles are unknown. We used array and exome sequencing data from 656 proband-parent trios to examine the contribution of common and rare variants to school performance, and by implication cognitive function, in schizophrenia. Parental transmission of common alleles contributing to higher educational attainment (p value = 0.00015; OR = 2.63) and intelligence (p value = 0.00009; OR = 2.80), but not to schizophrenia, were associated with higher proband school performance. No significant effects were seen for non-transmitted parental common alleles. Probands with lower school performance were enriched for damaging de novo coding variants in genes associated with developmental disorders (DD) (p value = 0.00026; OR = 11.6). Damaging, ultra-rare coding variants in DD genes that were transmitted or non-transmitted from parents, had no effects on school performance. Among probands with lower school performance, those with damaging de novo coding variants in DD genes had a higher rate of comorbid mild intellectual disability (p value = 0.0002; OR = 15.6). Overall, we provide evidence for rare and common genetic contributions to school performance in schizophrenia. The strong effects for damaging de novo coding variants in DD genes provide further evidence that cognitive impairment in schizophrenia has a shared aetiology with developmental disorders. Furthermore, we report no evidence in this sample that non-transmitted parental common alleles for cognitive traits contributed to school performance in schizophrenia via indirect effects on the environment.
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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。
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：
10.1192/bjp.bp.113.131052
发表时间：
2014-02
期刊：
The British journal of psychiatry : the journal of mental science
影响因子：
--
作者：
Rees E;Walters JT;Georgieva L;Isles AR;Chambert KD;Richards AL;Mahoney-Davies G;Legge SE;Moran JL;McCarroll SA;O'Donovan MC;Owen MJ;Kirov G
通讯作者：
Kirov G
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
影响因子：
6.9
作者：
MacCabe, J. H.;Lambe, M. P.;Hultman, C. M.
通讯作者：
Hultman, C. M.
影响因子：
9.2
作者：
Choi, Shing Wan;O'Reilly, Paul F.
通讯作者：
O'Reilly, Paul F.