A brief report: de novo copy number variants in children with attention deficit hyperactivity disorder
A brief report: de novo copy number variants in children with attention deficit hyperactivity disorder
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简短报告：注意力缺陷多动障碍儿童的从头拷贝数变异
DOI：
10.1101/2019.12.12.19014555
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Martin J
中科院分区：
文献类型：
--
作者：
Martin J
最近对注意缺陷多动障碍（ADHD）的病例对照遗传研究发现了常见和罕见的遗传风险等位基因，强调了这种神经发育障碍的多基因和复杂病因。对其他神经发育障碍的研究，如自闭症谱系障碍（ASD）、妥瑞氏症、发育迟缓/智力残疾和精神分裂症，表明可以通过研究非遗传性从头变异来识别特定的风险等位基因，并进一步了解疾病生物学。在这项研究中，我们旨在确定ADHD儿童的大新生拷贝数变异（CNVs）。确诊为ADHD的儿童及其父母进行基因分型并纳入本样本。我们使用PennCNV来召唤大的（大约200 kb） cnv，并识别出那些在先证者中存在而在两个亲生父母中都不存在的呼叫。在305个亲代三联中，我们在13个先证中检测到14个新生CNVs，突变率为4.6%，个体突变率为4.3%。这一比例高于已发表的对照组报告，与ASD、精神分裂症和图雷特症的观察结果相似。我们还发现了四个基因组位点（15q13.1-13.2重复，16p13.11重复，16p12.2缺失和22q11.21重复）的新生突变，这些位点先前与其他神经发育障碍有关，其中两个位点（16p13.11和22q11.21）也与病例对照ADHD研究有关。我们的研究补充了ADHD病例对照基因组分析，并表明需要进行更大规模的父母-后代三人遗传研究，以进一步了解ADHD的复杂病因。
Recent case–control genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated common and rare genetic risk alleles, highlighting the polygenic and complex aetiology of this neurodevelopmental disorder. Studies of other neurodevelopmental disorders, such as autism spectrum disorder (ASD), Tourette disorder, developmental delay/intellectual disability and schizophrenia indicate that identification of specific risk alleles and additional insights into disorder biology can be gained by studying non-inherited de novo variation. In this study, we aimed to identify large de novo copy number variants (CNVs) in children with ADHD. Children with a confirmed diagnosis of ADHD and their parents were genotyped and included in this sample. We used PennCNV to call large (>200 kb) CNVs and identified those calls that were present in the proband and absent in both biological parents. In 305 parent–offspring trios, we detected 14 de novo CNVs in 13 probands, giving a mutation rate of 4.6% and a per individual rate of 4.3%. This rate is higher than published reports in controls and similar to those observed for ASD, schizophrenia and Tourette disorder. We also identified de novo mutations at four genomic loci (15q13.1–13.2 duplication, 16p13.11 duplication, 16p12.2 deletion and 22q11.21 duplication) that have previously been implicated in other neurodevelopmental disorders, two of which (16p13.11 and 22q11.21) have also been implicated in case–control ADHD studies. Our study complements ADHD case–control genomic analyses and demonstrates the need for larger parent–offspring trio genetic studies to gain further insights into the complex aetiology of ADHD.
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影响因子：
0.9
作者：
Muhammed Ather;G. Salmon
通讯作者：
Muhammed Ather;G. Salmon
健康对照中的从头 CNV 发生率
DOI：
10.1101/857797
发表时间：
2019
期刊：
bioRxiv
影响因子：
--
作者：
J. Barone;Mathew Smith;K. Kendall;M. Owen;M. O’Donovan;G. Kirov
通讯作者：
G. Kirov
影响因子：
4.1
作者：
Tamhane Ashutosh;G. McGwin
通讯作者：
Tamhane Ashutosh;G. McGwin
影响因子：
30.8
作者：
Marshall CR;Howrigan DP;Merico D;Thiruvahindrapuram B;Wu W;Greer DS;Antaki D;Shetty A;Holmans PA;Pinto D;Gujral M;Brandler WM;Malhotra D;Wang Z;Fajarado KVF;Maile MS;Ripke S;Agartz I;Albus M;Alexander M;Amin F;Atkins J;Bacanu SA;Belliveau RA Jr;Bergen SE;Bertalan M;Bevilacqua E;Bigdeli TB;Black DW;Bruggeman R;Buccola NG;Buckner RL;Bulik-Sullivan B;Byerley W;Cahn W;Cai G;Cairns MJ;Campion D;Cantor RM;Carr VJ;Carrera N;Catts SV;Chambert KD;Cheng W;Cloninger CR;Cohen D;Cormican P;Craddock N;Crespo-Facorro B;Crowley JJ;Curtis D;Davidson M;Davis KL;Degenhardt F;Del Favero J;DeLisi LE;Dikeos D;Dinan T;Djurovic S;Donohoe G;Drapeau E;Duan J;Dudbridge F;Eichhammer P;Eriksson J;Escott-Price V;Essioux L;Fanous AH;Farh KH;Farrell MS;Frank J;Franke L;Freedman R;Freimer NB;Friedman JI;Forstner AJ;Fromer M;Genovese G;Georgieva L;Gershon ES;Giegling I;Giusti-Rodríguez P;Godard S;Goldstein JI;Gratten J;de Haan L;Hamshere ML;Hansen M;Hansen T;Haroutunian V;Hartmann AM;Henskens FA;Herms S;Hirschhorn JN;Hoffmann P;Hofman A;Huang H;Ikeda M;Joa I;Kähler AK;Kahn RS;Kalaydjieva L;Karjalainen J;Kavanagh D;Keller MC;Kelly BJ;Kennedy JL;Kim Y;Knowles JA;Konte B;Laurent C;Lee P;Lee SH;Legge SE;Lerer B;Levy DL;Liang KY;Lieberman J;Lönnqvist J;Loughland CM;Magnusson PKE;Maher BS;Maier W;Mallet J;Mattheisen M;Mattingsdal M;McCarley RW;McDonald C;McIntosh AM;Meier S;Meijer CJ;Melle I;Mesholam-Gately RI;Metspalu A;Michie PT;Milani L;Milanova V;Mokrab Y;Morris DW;Müller-Myhsok B;Murphy KC;Murray RM;Myin-Germeys I;Nenadic I;Nertney DA;Nestadt G;Nicodemus KK;Nisenbaum L;Nordin A;O'Callaghan E;O'Dushlaine C;Oh SY;Olincy A;Olsen L;O'Neill FA;Van Os J;Pantelis C;Papadimitriou GN;Parkhomenko E;Pato MT;Paunio T;Psychosis Endophenotypes International Consortium;Perkins DO;Pers TH;Pietiläinen O;Pimm J;Pocklington AJ;Powell J;Price A;Pulver AE;Purcell SM;Quested D;Rasmussen HB;Reichenberg A;Reimers MA;Richards AL;Roffman JL;Roussos P;Ruderfer DM;Salomaa V;Sanders AR;Savitz A;Schall U;Schulze TG;Schwab SG;Scolnick EM;Scott RJ;Seidman LJ;Shi J;Silverman JM;Smoller JW;Söderman E;Spencer CCA;Stahl EA;Strengman E;Strohmaier J;Stroup TS;Suvisaari J;Svrakic DM;Szatkiewicz JP;Thirumalai S;Tooney PA;Veijola J;Visscher PM;Waddington J;Walsh D;Webb BT;Weiser M;Wildenauer DB;Williams NM;Williams S;Witt SH;Wolen AR;Wormley BK;Wray NR;Wu JQ;Zai CC;Adolfsson R;Andreassen OA;Blackwood DHR;Bramon E;Buxbaum JD;Cichon S;Collier DA;Corvin A;Daly MJ;Darvasi A;Domenici E;Esko T;Gejman PV;Gill M;Gurling H;Hultman CM;Iwata N;Jablensky AV;Jönsson EG;Kendler KS;Kirov G;Knight J;Levinson DF;Li QS;McCarroll SA;McQuillin A;Moran JL;Mowry BJ;Nöthen MM;Ophoff RA;Owen MJ;Palotie A;Pato CN;Petryshen TL;Posthuma D;Rietschel M;Riley BP;Rujescu D;Sklar P;St Clair D;Walters JTR;Werge T;Sullivan PF;O'Donovan MC;Scherer SW;Neale BM;Sebat J;CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium
通讯作者：
CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium
影响因子：
25.8
作者：
Rees, Elliott;Kendall, Kimberley;Pardinas, Antonio F.;Legge, Sophie E.;Pocklington, Andrew;Escott-Price, Valentina;MacCabe, James H.;Collier, David A.;Holmans, Peter;O'Donovan, Michael C.;Owen, Michael J.;Walters, James T. R.;Kirov, George
通讯作者：
Kirov, George