The penetrance of copy number variations for schizophrenia and developmental delay.
The penetrance of copy number variations for schizophrenia and developmental delay.
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DOI：
10.1016/j.biopsych.2013.07.022
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发表时间：
2014-03-01
影响因子：
10.6
通讯作者：
Owen, Michael J.
中科院分区：
文献类型：
--
作者：
Kirov, George;Rees, Elliott;Walters, James T. R.;Escott-Price, Valentina;Georgieva, Lyudmila;Richards, Alexander L.;Chambert, Kimberly D.;Davies, Gerwyn;Legge, Sophie E.;Moran, Jennifer L.;McCarroll, Steven A.;O'Donovan, Michael C.;Owen, Michael J.
一些复发性拷贝数变异（CNVs）已被证明会增加患精神分裂症（SCZ）、发育迟缓（DD）、自闭症谱系障碍（ASD）和各种先天性畸形（CM）的风险。它们对SCZ的外显率估计是适度的。然而，他们在SCZ或DD/ASD/CM的外显率之间的比较，或对任何这些疾病的总外显率的估计尚未做出。我们使用了目前最大的SCZ和DD/ASD/CM研究的数据，包括6882例新样本和6316例对照，以估计70个相关CNVs的频率，包括这些疾病的携带者、健康对照和普通人群。在这些频率的基础上，我们估计它们的外显率。我们还估计了对CNVs的选择压力强度，并将其与它们的总体外显率相关联。与SCZ相比，DD/ASD/CM中几乎所有的CNVs率都更高。在DD/ASD/CM组中，CNVs的外显率至少高出几倍。scz相关CNVs在任何疾病中的总体外显率都很高，范围在10.6%到100%之间。与SCZ相关的CNVs具有高致病性。CNVs增加的风险主要是发生早发性疾病，如DD/ASD/CM，而不是SCZ。CNVs的外显率与其选择系数密切相关。外显率的改进估计将为遗传咨询提供关键信息。
Several recurrent copy number variants (CNVs) have been shown to increase the risk of developing schizophrenia (SCZ), developmental delay (DD), autism spectrum disorders (ASD) and various congenital malformations (CM). Their penetrance for SCZ has been estimated to be modest. However, comparisons between their penetrance for SCZ or DD/ASD/CM, or estimates of the total penetrance for any of these disorders have not been made yet. We use data from the largest available studies on SCZ and DD/ASD/CM, including a new sample of 6882 cases and 6316 controls, to estimate the frequencies of 70 implicated CNVs, in carriers with these disorders, in healthy controls and in the general population. On the basis of these frequencies we estimate their penetrance. We also estimate the strength of the selection pressure against CNVs and correlate this against their overall penetrance. The rates of nearly all CNVs are higher in DD/ASD/CM, compared to SCZ. The penetrance of CNVs is at least several times higher for the development of a disorder from the group of DD/ASD/CM. The overall penetrance of SCZ-associated CNVs for developing any disorder is high, ranging between 10.6% and 100%. CNVs associated with SCZ have high pathogenicity. The majority of the increased risk conferred by CNVs is towards the development of an earlier-onset disorder, such as DD/ASD/CM, rather than SCZ. The penetrance of CNVs correlates strongly with their selection coefficients. The improved estimates of penetrance will provide crucial information for genetic counselling.
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影响因子：
4
作者：
Miller DT;Shen Y;Weiss LA;Korn J;Anselm I;Bridgemohan C;Cox GF;Dickinson H;Gentile J;Harris DJ;Hegde V;Hundley R;Khwaja O;Kothare S;Luedke C;Nasir R;Poduri A;Prasad K;Raffalli P;Reinhard A;Smith SE;Sobeih MM;Soul JS;Stoler J;Takeoka M;Tan WH;Thakuria J;Wolff R;Yusupov R;Gusella JF;Daly MJ;Wu BL
通讯作者：
Wu BL
影响因子：
30.8
作者：
Helbig I;Mefford HC;Sharp AJ;Guipponi M;Fichera M;Franke A;Muhle H;de Kovel C;Baker C;von Spiczak S;Kron KL;Steinich I;Kleefuss-Lie AA;Leu C;Gaus V;Schmitz B;Klein KM;Reif PS;Rosenow F;Weber Y;Lerche H;Zimprich F;Urak L;Fuchs K;Feucht M;Genton P;Thomas P;Visscher F;de Haan GJ;Møller RS;Hjalgrim H;Luciano D;Wittig M;Nothnagel M;Elger CE;Nürnberg P;Romano C;Malafosse A;Koeleman BP;Lindhout D;Stephani U;Schreiber S;Eichler EE;Sander T
通讯作者：
Sander T
影响因子：
168.9
作者：
Williams, Nigel M.;Zaharieva, Irina;Martin, Andrew;Langley, Kate;Mantripragada, Kiran;Fossdal, Ragnheidur;Stefansson, Hreinn;Stefansson, Karl;Magnusson, Pall;Gudmundsson, Olafur O.;Gustafsson, Omar;Holmans, Peter;Owen, Michael J.;O'Donovan, Michael;Thapar, Anita
通讯作者：
Thapar, Anita
影响因子：
30.8
作者：
Sharp, Andrew J.;Mefford, Heather C.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
10.5
作者：
Baron-Cohen, Simon;Scott, Fiona J.;Brayne, Carol
通讯作者：
Brayne, Carol