Association of Genetic Risk Variants With Attention-Deficit/Hyperactivity Disorder Trajectories in the General Population.
Association of Genetic Risk Variants With Attention-Deficit/Hyperactivity Disorder Trajectories in the General Population.
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一般人群中遗传风险变异与注意力缺陷/多动症障碍轨迹的关联。
DOI：
10.1001/jamapsychiatry.2016.2817
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发表时间：
2016-12-01
期刊：
影响因子：
25.8
通讯作者：
Thapar A
中科院分区：
文献类型：
--
作者：
Riglin L;Collishaw S;Thapar AK;Dalsgaard S;Langley K;Smith GD;Stergiakouli E;Maughan B;O'Donovan MC;Thapar A
注意力缺陷多动障碍（ADHD）是一种遗传性神经发育障碍，与其他儿童神经发育障碍有临床和遗传重叠。ADHD症状的水平通常在儿童和青少年时期下降，尽管对某些人来说仍然升高。症状持续和下降的决定因素尚未完全了解。为了检验ADHD的遗传风险变异负荷（以多基因风险评分[PRS]为索引），而不是其他精神疾病，与儿童期和青春期基于人群的ADHD症状轨迹相关的假设，并检查ADHD的较高遗传易感性是否与儿童期其他神经发育障碍（多发病）的总数相关。雅芳家长和儿童纵向研究是一项正在进行的前瞻性人群队列研究，自1990年9月6日以来，已收集了14701名儿童的数据，其中包括9757名儿童在多个时间点的ADHD症状数据。主要暴露变量PRS是使用精神病基因组学联盟的全基因组关联研究结果生成的。儿童期多项运动障碍评分（7 - 9岁）是通过已知与ADHD共享遗传易感性的4个领域的总损伤来测量的：智商，社交，语用语言和行为。数据分析于2016年3月1日至9月8日进行。4 - 17岁（7个时间点）的注意力缺陷/多动障碍症状轨迹。在多个时间点（年龄范围，4 - 17岁; 4968名男孩和4789名女孩）的9757名儿童中，确定了4种ADHD症状轨迹：轻度（82.6%），中度（7.7%），儿童期有限（5.8%）和持续性（3.9%）。ADHD的平均（SE）PRS在持续性轨迹中的儿童中更高（0.254 [0.069]）与其他3种轨迹相比（低，-0. 018 [0. 014]，P <0. 001，比值比1. 31;中，0. 054 [0. 055]，P = 0. 03，比值比1. 22;和儿童期限制，0.017 [0.060]，，P =.01，优势比，1.27）。研究结果是特定于多动症的PRS;其他精神疾病的PRS在不同轨迹之间没有差异。在持续性轨迹中，患有多项抑郁症的儿童比例也最高（42.5%; 95% CI，33.9%-51.1%; P <0.001），并且与独立于PRS的ADHD症状的持续性相关。在一般人群中，ADHD症状在儿童期和青春期的持续性与ADHD的较高PRS相关。儿童期多发病也与ADHD症状的持续存在有关，这可能有助于识别ADHD儿童，其症状最有可能持续到青春期。
Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder that shows clinical and genetic overlap with other childhood neurodevelopmental disorders. Levels of ADHD symptoms typically decline across childhood and adolescence, although they remain elevated for some individuals. The determinants of symptom persistence and decline are not yet fully understood. To test the hypothesis that genetic risk variant load for ADHD (indexed by polygenic risk scores [PRS]), but not for other psychiatric disorders, is associated with population-based ADHD symptom trajectories across childhood and adolescence, and to examine whether higher genetic liability for ADHD is correlated with total number of additional neurodevelopmental disorders (multimorbidity) in childhood. The Avon Longitudinal Study of Parents and Children, an ongoing prospective population-based cohort study, has been collecting data on 14 701 children, including 9757 with data on symptoms of ADHD at multiple time points, since September 6, 1990. The primary exposure variables, PRS, were generated using results of a genome-wide association study from the Psychiatric Genomics Consortium. Childhood multimorbidity scores (ages 7-9 years) were measured by total impairments in 4 domains known to share genetic liability with ADHD: IQ, social communication, pragmatic language, and conduct. Data analysis was conducted from March 1 to September 8, 2016. Attention-deficit/hyperactivity disorder symptom trajectories from ages 4 to 17 years (7 time points). Among 9757 children with data on symptoms of ADHD at multiple time points (age range, 4-17 years; 4968 boys and 4789 girls), 4 ADHD symptom trajectories were identified: low (82.6%), intermediate (7.7%), childhood-limited (5.8%), and persistent (3.9%). Mean (SE) PRS for ADHD were higher in children in the persistent trajectory (0.254 [0.069]) compared with each of the other 3 trajectories (low, –0.018 [0.014], , P < .001, odds ratio, 1.31; intermediate, 0.054 [0.055], , P = .03, odds ratio, 1.22; and childhood-limited, 0.017 [0.060], , P = .01, odds ratio, 1.27). Findings were specific to PRS for ADHD; PRS for other psychiatric conditions did not differ across trajectories. The proportion of children with multimorbidity was also highest in those in the persistent trajectory (42.5%; 95% CI, 33.9%-51.1%; P < .001) and was associated with persistence of ADHD symptoms independent of PRS. Persistence of ADHD symptoms across childhood and adolescence in the general population is associated with higher PRS for ADHD. Childhood multimorbidity was also associated with persistence of ADHD symptoms and may help to identify children with ADHD whose symptoms are most likely to continue into adolescence.
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影响因子：
25.8
作者：
Chang, Zheng;Lichtenstein, Paul;Larsson, Henrik
通讯作者：
Larsson, Henrik
影响因子：
11
作者：
Franke, B.;Faraone, S. V.;Asherson, P.;Buitelaar, J.;Bau, C. H. D.;Ramos-Quiroga, J. A.;Mick, E.;Grevet, E. H.;Johansson, S.;Haavik, J.;Lesch, K-P;Cormand, B.;Reif, A.
通讯作者：
Reif, A.
DOI：
10.1176/appi.ajp.2013.12081129
发表时间：
2013-08
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Hamshere ML;Langley K;Martin J;Agha SS;Stergiakouli E;Anney RJ;Buitelaar J;Faraone SV;Lesch KP;Neale BM;Franke B;Sonuga-Barke E;Asherson P;Merwood A;Kuntsi J;Medland SE;Ripke S;Steinhausen HC;Freitag C;Reif A;Renner TJ;Romanos M;Romanos J;Warnke A;Meyer J;Palmason H;Vasquez AA;Lambregts-Rommelse N;Roeyers H;Biederman J;Doyle AE;Hakonarson H;Rothenberger A;Banaschewski T;Oades RD;McGough JJ;Kent L;Williams N;Owen MJ;Holmans P;O'Donovan MC;Thapar A
通讯作者：
Thapar A
影响因子：
30.8
作者：
Lee, S. Hong;Ripke, Stephan;Neale, Benjamin M.;Faraone, Stephen V.;Purcell, Shaun M.;Perlis, Roy H.;Mowry, Bryan J.;Thapar, Anita;Goddard, Michael E.;Witte, John S.;Absher, Devin;Agartz, Ingrid;Akil, Huda;Amin, Farooq;Andreassen, Ole A.;Anjorin, Adebayo;Anney, Richard;Anttila, Verneri;Arking, Dan E.;Asherson, Philip;Azevedo, Maria H.;Backlund, Lena;Badner, Judith A.;Bailey, Anthony J.;Banaschewski, Tobias;Barchas, Jack D.;Barnes, Michael R.;Barrett, Thomas B.;Bass, Nicholas;Battaglia, Agatino;Bauer, Michael;Bayes, Monica;Bellivier, Frank;Bergen, Sarah E.;Berrettini, Wade;Betancur, Catalina;Bettecken, Thomas;Biederman, Joseph;Binder, Elisabeth B.;Black, Donald W.;Blackwood, Douglas H. R.;Bloss, Cinnamon S.;Boehnke, Michael;Boomsma, Dorret I.;Breen, Gerome;Breuer, Rene;Bruggeman, Richard;Cormican, Paul;Buccola, Nancy G.;Buitelaar, Jan K.;Bunney, William E.;Buxbaum, Joseph D.;Byerley, William F.;Byrne, Enda M.;Caesar, Sian;Cahn, Wiepke;Cantor, Rita M.;Casas, Miguel;Chakravarti, Aravinda;Chambert, Kimberly;Choudhury, Khalid;Cichon, Sven;Cloninger, C. Robert;Collier, David A.;Cook, Edwin H.;Coon, Hilary;Cormand, Bru;Corvin, Aiden;Coryell, William H.;Craig, David W.;Craig, Ian W.;Crosbie, Jennifer;Cuccaro, Michael L.;Curtis, David;Czamara, Darina;Datta, Susmita;Dawson, Geraldine;Day, Richard;De Geus, Eco J.;Degenhardt, Franziska;Djurovic, Srdjan;Donohoe, Gary J.;Doyle, Alysa E.;Duan, Jubao;Dudbridge, Frank;Duketis, Eftichia;Ebstein, Richard P.;Edenberg, Howard J.;Elia, Josephine;Ennis, Sean;Etain, Bruno;Fanous, Ayman;Farmer, Anne E.;Ferrier, I. Nicol;Flickinger, Matthew;Fombonne, Eric;Foroud, Tatiana;Frank, Josef;Franke, Barbara;Fraser, Christine;Freedman, Robert;Freimer, Nelson B.;Freitag, Christine M.;Friedl, Marion;Frisen, Louise;Gallagher, Louise;Gejman, Pablo V.;Georgieva, Lyudmila;Gershon, Elliot S.;Geschwind, Daniel H.;Giegling, Ina;Gill, Michael;Gordon, Scott D.;Gordon-Smith, Katherine;Green, Elaine K.;Greenwood, Tiffany A.;Grice, Dorothy E.;Gross, Magdalena;Grozeva, Detelina;Guan, Weihua;Gurling, Hugh;De Haan, Lieuwe;Haines, Jonathan L.;Hakonarson, Hakon;Hallmayer, Joachim;Hamilton, Steven P.;Hamshere, Marian L.;Hansen, Thomas F.;Hartmann, Annette M.;Hautzinger, Martin;Heath, Andrew C.;Henders, Anjali K.;Herms, Stefan;Hickie, Ian B.;Hipolito, Maria;Hoefels, Susanne;Holmans, Peter A.;Holsboer, Florian;Hoogendijk, Witte J.;Hottenga, Jouke-Jan;Hultman, Christina M.;Hus, Vanessa;Ingason, Andres;Ising, Marcus;Jamain, Stephane;Jones, Edward G.;Jones, Ian;Jones, Lisa;Tzeng, Jung-Ying;Kaehler, Anna K.;Kahn, Rene S.;Kandaswamy, Radhika;Keller, Matthew C.;Kennedy, James L.;Kenny, Elaine;Kent, Lindsey;Kim, Yunjung;Kirov, George K.;Klauck, Sabine M.;Klei, Lambertus;Knowles, James A.;Kohli, Martin A.;Koller, Daniel L.;Konte, Bettina;Korszun, Ania;Krabbendam, Lydia;Krasucki, Robert;Kuntsi, Jonna;Kwan, Phoenix;Landen, Mikael;Langstrom, Niklas;Lathrop, Mark;Lawrence, Jacob;Lawson, William B.;Leboyer, Marion;Ledbetter, David H.;Lee, Phil H.;Lencz, Todd;Lesch, Klaus-Peter;Levinson, Douglas F.;Lewis, Cathryn M.;Li, Jun;Lichtenstein, Paul;Lieberman, Jeffrey A.;Lin, Dan-Yu;Linszen, Don H.;Liu, Chunyu;Lohoff, Falk W.;Loo, Sandra K.;Lord, Catherine;Lowe, Jennifer K.;Lucae, Susanne;MacIntyre, Donald J.;Madden, Pamela A. F.;Maestrini, Elena;Magnusson, Patrik K. E.;Mahon, Pamela B.;Maier, Wolfgang;Malhotra, Anil K.;Mane, Shrikant M.;Martin, Christa L.;Martin, Nicholas G.;Mattheisen, Manuel;Matthews, Keith;Mattingsdal, Morten;McCarroll, Steven A.;McGhee, Kevin A.;McGough, James J.;McGrath, Patrick J.;McGuffin, Peter;McInnis, Melvin G.;McIntosh, Andrew;McKinney, Rebecca;McLean, Alan W.;McMahon, Francis J.;McMahon, William M.;McQuillin, Andrew;Medeiros, Helena;Medland, Sarah E.;Meier, Sandra;Melle, Ingrid;Meng, Fan;Meyer, Jobst;Middeldorp, Christel M.;Middleton, Lefkos;Milanova, Vihra;Miranda, Ana;Monaco, Anthony P.;Montgomery, Grant W.;Moran, Jennifer L.;Moreno-De-Luca, Daniel;Morken, Gunnar;Morris, Derek W.;Morrow, Eric M.;Moskvina, Valentina;Muglia, Pierandrea;Muehleisen, Thomas W.;Muir, Walter J.;Mueller-Myhsok, Bertram;Murtha, Michael;Myers, Richard M.;Myin-Germeys, Inez;Neale, Michael C.;Nelson, Stan F.;Nievergelt, Caroline M.;Nikolov, Ivan;Nimgaonkar, Vishwajit;Nolen, Willem A.;Noethen, Markus M.;Nurnberger, John I.;Nwulia, Evaristus A.;Nyholt, Dale R.;O'Dushlaine, Colm;Oades, Robert D.;Olincy, Ann;Oliveira, Guiomar;Olsen, Line;Ophoff, Roel A.;Osby, Urban;Owen, Michael J.;Palotie, Aarno;Parr, Jeremy R.;Paterson, Andrew D.;Pato, Carlos N.;Pato, Michele T.;Penninx, Brenda W.;Pergadia, Michele L.;Pericak-Vance, Margaret A.;Pickard, Benjamin S.;Pimm, Jonathan;Piven, Joseph;Posthuma, Danielle;Potash, James B.;Poustka, Fritz;Propping, Peter;Puri, Vinay;Quested, Digby J.;Quinn, Emma M.;Antoni Ramos-Quiroga, Josep;Rasmussen, Henrik B.;Raychaudhuri, Soumya;Rehnstroem, Karola;Reif, Andreas;Ribases, Marta;Rice, John P.;Rietschel, Marcella;Roeder, Kathryn;Roeyers, Herbert;Rossin, Lizzy;Rothenberger, Aribert;Rouleau, Guy;Ruderfer, Douglas;Rujescu, Dan;Sanders, Alan R.;Sanders, Stephan J.;Santangelo, Susan L.;Sergeant, Joseph A.;Schachar, Russell;Schalling, Martin;Schatzberg, Alan F.;Scheftner, William A.;Schellenberg, Gerard D.;Scherer, Stephen W.;Schork, Nicholas J.;Schulze, Thomas G.;Schumacher, Johannes;Schwarz, Markus;Scolnick, Edward;Scott, Laura J.;Shi, Jianxin;Shilling, Paul D.;Shyn, Stanley I.;Silverman, Jeremy M.;Slager, Susan L.;Smalley, Susan L.;Smit, Johannes H.;Smith, Erin N.;Sonuga-Barke, Edmund J. S.;St Clair, David;State, Matthew;Steffens, Michael;Steinhausen, Hans-Christoph;Strauss, John S.;Strohmaier, Jana;Stroup, T. Scott;Sutcliffe, James S.;Szatmari, Peter;Szelinger, Szabocls;Thirumalai, Srinivasa;Thompson, Robert C.;Todorov, Alexandre A.;Tozzi, Federica;Treutlein, Jens;Uhr, Manfred;van den Oord, Edwin J. C. G.;Van Grootheest, Gerard;Van Os, Jim;Vicente, Astrid M.;Vieland, Veronica J.;Vincent, John B.;Visscher, Peter M.;Walsh, Christopher A.;Wassink, Thomas H.;Watson, Stanley J.;Weissman, Myrna M.;Werge, Thomas;Wienker, Thomas F.;Wijsman, Ellen M.;Willemsen, Gonneke;Williams, Nigel;Willsey, A. Jeremy;Witt, Stephanie H.;Xu, Wei;Young, Allan H.;Yu, Timothy W.;Zammit, Stanley;Zandi, Peter P.;Zhang, Peng;Zitman, Frans G.;Zoellner, Sebastian;Devlin, Bernie;Kelsoe, John R.;Sklar, Pamela;Daly, Mark J.;O'Donovan, Michael C.;Craddock, Nicholas;Sullivan, Patrick F.;Smoller, Jordan W.;Kendler, Kenneth S.;Wray, Naomi R.
通讯作者：
Wray, Naomi R.
影响因子：
10.6
作者：
Lara, Carmen;Fayyad, John;Sampson, Nancy
通讯作者：
Sampson, Nancy