Genetic associations with childhood brain growth, defined in two longitudinal cohorts.
Genetic associations with childhood brain growth, defined in two longitudinal cohorts.
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DOI：
10.1002/gepi.22122
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发表时间：
2018-06
影响因子：
2.1
通讯作者：
Shaw P
中科院分区：
文献类型：
--
作者：
Szekely E;Schwantes-An TL;Justice CM;Sabourin JA;Jansen PR;Muetzel RL;Sharp W;Tiemeier H;Sung H;White TJ;Wilson AF;Shaw P
全基因组关联研究（GWAS）正在通过横断面解剖磁共振成像（aMRI）来揭示成人脑神经解剖学的遗传学。然而，塑造儿童大脑发育的遗传机制在很大程度上尚未被探索。在这项研究中，我们确定了与纵向aMRI定义的儿童大脑发育相关的常见遗传变异。在2个队列中确定全基因组SNP数据：一个针对注意力缺陷/多动障碍（ADHD）富集（LONG队列：458名参与者; 119名ADHD），另一个来自基于人群的队列（R代：257名参与者）。对来自两个aMRI的所有个体定义大脑主要区域（大脑皮质、白色物质、基底节和小脑）和一个感兴趣区域（右侧前额叶皮质）的生长，并进行全基因组关联研究和途径分析。此外，在LONG队列中确定了ADHD多基因风险与脑生长之间的相关性。对于白色物质生长，GWAS荟萃分析确定了全基因组显著的基因间SNP（rs 12386571，p = 9.09x10−9），接近AKR 1B 10。该基因是醛酮还原酶超家族的一部分，并显示神经表达。在为诊断ADHD而富集的LONG队列中，未检测到神经通路的富集，ADHD的多基因风险与脑生长表型无关。该研究说明了使用一种新的脑生长表型定义在体内进行进一步的研究。
Genome-wide association studies (GWAS) are unraveling the genetics of adult brain neuroanatomy as measured by cross-sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI. Genome-wide SNP data were determined in 2 cohorts: one enriched for attention-deficit/hyperactivity disorder (ADHD) (LONG cohort: 458 participants; 119 with ADHD) and the other from a population-based cohort (Generation R: 257 participants). The growth of the brain’s major regions (cerebral cortex, white matter, basal ganglia and cerebellum) and one region of interest (the right lateral prefrontal cortex) were defined on all individuals from two aMRIs, and a genome-wide association study and a pathway analysis were performed. In addition, association between polygenic risk for ADHD and brain growth was determined for the LONG cohort. For white matter growth, GWAS meta-analysis identified a genome-wide significant intergenic SNP (rs12386571, p = 9.09x10−9), near AKR1B10. This gene is part of the aldo-keto reductase superfamily and shows neural expression. No enrichment of neural pathways was detected and polygenic risk for ADHD was not associated with the brain growth phenotypes in the LONG cohort that was enriched for the diagnosis of ADHD. The study illustrates the use of a novel brain growth phenotype defined in vivo for further study.
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DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
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：
11
作者：
Di Martino, A.;Yan, C-G;Li, Q.;Denio, E.;Castellanos, F. X.;Alaerts, K.;Anderson, J. S.;Assaf, M.;Bookheimer, S. Y.;Dapretto, M.;Deen, B.;Delmonte, S.;Dinstein, I.;Ertl-Wagner, B.;Fair, D. A.;Gallagher, L.;Kennedy, D. P.;Keown, C. L.;Keysers, C.;Lainhart, J. E.;Lord, C.;Luna, B.;Menon, V.;Minshew, N. J.;Monk, C. S.;Mueller, S.;Mueller, R. A.;Nebel, M. B.;Nigg, J. T.;O'Hearn, K.;Pelphrey, K. A.;Peltier, S. J.;Rudie, J. D.;Sunaert, S.;Thioux, M.;Tyszka, J. M.;Uddin, L. Q.;Verhoeven, J. S.;Wenderoth, N.;Wiggins, J. L.;Mostofsky, S. H.;Milham, M. P.
通讯作者：
Milham, M. P.
影响因子：
11.2
作者：
Friedman, Jennifer;Roze, Emmanuel;Blau, Nenad
通讯作者：
Blau, Nenad
影响因子：
5.3
作者：
Higuera-Matas, A.;Montoya, G. L.;Ambrosio, E.
通讯作者：
Ambrosio, E.