Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.
Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.
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DOI：
10.1001/jamapsychiatry.2015.2123
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发表时间：
2016-01
期刊：
影响因子：
25.8
通讯作者：
Simons Variation in Individuals Project (VIP) Consortium
中科院分区：
文献类型：
--
作者：
D'Angelo D;Lebon S;Chen Q;Martin-Brevet S;Snyder LG;Hippolyte L;Hanson E;Maillard AM;Faucett WA;Macé A;Pain A;Bernier R;Chawner SJ;David A;Andrieux J;Aylward E;Baujat G;Caldeira I;Conus P;Ferrari C;Forzano F;Gérard M;Goin-Kochel RP;Grant E;Hunter JV;Isidor B;Jacquette A;Jønch AE;Keren B;Lacombe D;Le Caignec C;Martin CL;Männik K;Metspalu A;Mignot C;Mukherjee P;Owen MJ;Passeggeri M;Rooryck-Thambo C;Rosenfeld JA;Spence SJ;Steinman KJ;Tjernagel J;Van Haelst M;Shen Y;Draganski B;Sherr EH;Ledbetter DH;van den Bree MB;Beckmann JS;Spiro JE;Reymond A;Jacquemont S;Chung WK;Cardiff University Experiences of Children With Copy Number Variants (ECHO) Study;16p11.2 European Consortium;Simons Variation in Individuals Project (VIP) Consortium
16p11.2 BP 4-BP 5重复是最常与自闭症谱系障碍（ASD）、精神分裂症和合并症（如体重指数（BMI）降低）相关的拷贝数变异。描述16p11.2重复对认知、行为、医学和人体测量学特征的影响，并通过系统比较重复携带者和相互缺失携带者（他们也有ASD风险）的结果，了解这些影响的特异性。这项国际队列研究共有1006名研究参与者，将270名重复携带者与其102名家庭内对照个体、390名相互缺失携带者以及来自欧洲和北美队列的244名缺失对照进行了比较。数据收集时间为2010年8月1日至2015年5月31日，分析时间为2015年1月1日至8月14日。采用线性混合模型，通过与非携带者亲属的比较，估计重复和缺失对临床性状的影响。全面智商（FSIQ），非语言智商和语言智商的结果; ASD或其他DSM-IV诊断的存在; BMI;头围;和医疗数据。在1006名研究参与者中，重复与先证者携带者和非携带者亲属的平均FSIQ评分低26.3分相关，而非先证者携带者的平均FSIQ评分较低（16.2-11.4分）。删除的平均总体效果相似（-22.1分; P < .001）。然而，发现FSIQ的广泛变化，与缺失组相比，FSIQ分数非常低（≤40）和高于平均值（>100）的比例分别增加了19.4倍和2.0倍（P < .001）。父母FSIQ预测了这种变化的一部分（遗传先证者中约36.0%）。虽然ASD的频率在缺失和重复先证者携带者中相似（分别为16.0%和20.0%），但ASD重复先证者的FSIQ显著较低（26.3分）。重复携带者的头围和BMI测量值也较低，这与以前的研究结果一致。重复对认知的平均影响与相互缺失相似，但重复的方差显著更高，严重和轻度亚组未观察到缺失。这些结果表明，额外的遗传和家族因素有助于这种变异性。需要进一步的研究来描述认知缺陷的预测因素。
The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (−22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.
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影响因子：
30.8
作者：
McCarthy, Shane E.;Makarov, Vladimir;Kirov, George;Addington, Anjene M.;McClellan, Jon;Yoon, Seungtai;Perkins, Diana O.;Dickel, Diane E.;Kusenda, Mary;Krastoshevsky, Olga;Krause, Verena;Kumar, Ravinesh A.;Grozeva, Detelina;Malhotra, Dheeraj;Walsh, Tom;Zackai, Elaine H.;Kaplan, Paige;Ganesh, Jaya;Krantz, Ian D.;Spinner, Nancy B.;Roccanova, Patricia;Bhandari, Abhishek;Pavon, Kevin;Lakshmi, B.;Leotta, Anthony;Kendall, Jude;Lee, Yoon-ha;Vacic, Vladimir;Gary, Sydney;Iakoucheva, Lilia M.;Crow, Timothy J.;Christian, Susan L.;Lieberman, Jeffrey A.;Stroup, T. Scott;Lehtimaki, Terho;Puura, Kaija;Haldeman-Englert, Chad;Pearl, Justin;Goodell, Meredith;Willour, Virginia L.;DeRosse, Pamela;Steele, Jo;Kassem, Layla;Wolff, Jessica;Chitkara, Nisha;McMahon, Francis J.;Malhotra, Anil K.;Potash, James B.;Schulze, Thomas G.;Noethen, Markus M.;Cichon, Sven;Rietschel, Marcella;Leibenluft, Ellen;Kustanovich, Vlad;Lajonchere, Clara M.;Sutcliffe, James S.;Skuse, David;Gill, Michael;Gallagher, Louise;Mendell, Nancy R.;Craddock, Nick;Owen, Michael J.;O'Donovan, Michael C.;Shaikh, Tamim H.;Susser, Ezra;DeLisi, Lynn E.;Sullivan, Patrick F.;Deutsch, Curtis K.;Rapoport, Judith;Levy, Deborah L.;King, Mary-Claire;Sebat, Jonathan
通讯作者：
Sebat, Jonathan
影响因子：
11
作者：
Maillard, A. M.;Ruef, A.;Pizzagalli, F.;Migliavacca, E.;Hippolyte, L.;Adaszewski, S.;Dukart, J.;Ferrari, C.;Conus, P.;Maennik, K.;Zazhytska, M.;Siffredi, V.;Maeder, P.;Kutalik, Z.;Kherif, F.;Hadjikhani, N.;Beckmann, J. S.;Reymond, A.;Draganski, B.;Jacquemont, S.
通讯作者：
Jacquemont, S.
影响因子：
158.5
作者：
Weiss, Lauren A.;Shen, Yiping;Daly, Mark J.
通讯作者：
Daly, Mark J.
影响因子：
2
作者：
Al-Kateb, Hussam;Khanna, Geetika;Shinawi, Marwan
通讯作者：
Shinawi, Marwan
影响因子：
25.8
作者：
Moreno-De-Luca, Andres;Evans, David W.;Ledbetter, David H.
通讯作者：
Ledbetter, David H.