DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder.
DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder.
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DOI：
10.1371/journal.pone.0035424
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Le Hellard S
中科院分区：
文献类型：
--
作者：
Håvik B;Degenhardt FA;Johansson S;Fernandes CP;Hinney A;Scherag A;Lybæk H;Djurovic S;Christoforou A;Ersland KM;Giddaluru S;O'Donovan MC;Owen MJ;Craddock N;Mühleisen TW;Mattheisen M;Schimmelmann BG;Renner T;Warnke A;Herpertz-Dahlmann B;Sinzig J;Albayrak Ö;Rietschel M;Nöthen MM;Bramham CR;Werge T;Hebebrand J;Haavik J;Andreassen OA;Cichon S;Steen VM;Le Hellard S
双皮质素和钙调素样激酶1（DCLK 1）与突触可塑性和神经发育有关。DCLK 1的遗传变异与认知特征有关，特别是言语记忆和一般认知。我们研究了DCLK 1变异体在三种具有神经认知功能障碍的精神疾病中的作用：精神分裂症（SCZ），双相情感障碍（BP）和注意缺陷多动障碍（ADHD）。我们挖掘了六个基因组范围内的关联研究（GWAS），这些研究可以通过实验或合作获得;三个用于BP，两个用于SCZ，一个用于ADHD。我们还对SCZ、BP或ADHD病例的其他样本以及未进行全基因组分型的对照组进行了DCLK 1区域的基因分型。总共分析了9895例受试者，包括5308例正常对照和4,587例患者（1,125例SCZ，2,496例BP和966例ADHD）。几种DCLK 1变异体与不同样本中的疾病表型相关。在内含子3中观察到rs7989807的主要效应，这与单独的SCZ密切相关，当SCZ和ADHD合并时甚至更密切相关（P值分别为4×10−5和4×10−6）。 还观察到与内含子3（SCZ、ADHD和BP的组合）、内含子19（SCZ+BP）和3′UTR（SCZ+BP）中的其他标记的关联。我们的研究结果表明，DCLK 1的遗传变异与SCZ相关，在较小程度上与ADHD和BP相关。有趣的是，当SCZ和ADHD一起考虑时，这种关联最强，表明共同的遗传易感性。鉴于先前发现DCLK 1变体与认知特征相关，这些结果与DCLK 1在神经发育和突触可塑性中的作用一致。
Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD). Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4×10−5 and 4×10−6, respectively). Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3′UTR (SCZ+BP). Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity.
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影响因子：
6.4
作者：
Banaschewski, Tobias;Becker, Katja;Scherag, Susann;Franke, Barbara;Coghill, David
通讯作者：
Coghill, David
影响因子：
4.5
作者：
de la Serna, Elena;Baeza, Inmaculada;Castro-Fornieles, Josefina
通讯作者：
Castro-Fornieles, Josefina
影响因子：
4.8
作者：
Burgess, HA;Reiner, O
通讯作者：
Reiner, O
影响因子：
9.8
作者：
Cichon, Sven;Muehleisen, Thomas W.;Noethen, Markus M.
通讯作者：
Noethen, Markus M.
影响因子：
11
作者：
Green, M. J.;Matheson, S. L.;Carr, V. J.
通讯作者：
Carr, V. J.