High loading of polygenic risk for ADHD in children with comorbid aggression.
High loading of polygenic risk for ADHD in children with comorbid aggression.
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DOI：
10.1176/appi.ajp.2013.12081129
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Thapar A
中科院分区：
文献类型：
--
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
尽管注意缺陷多动障碍（ADHD）具有高度遗传性，但全基因组关联研究（GWAS）尚未发现任何导致风险的常见遗传变异。有证据表明，多动症儿童的攻击或行为障碍指数较高的基因负荷和临床严重程度。作者研究了作为ADHD多基因评分的常见遗传变异是否在患有共病性品行障碍的儿童中特别丰富。在独立的ADHD样本（452例受试者，5081例对照受试者）中计算ADHD GWAS荟萃分析得出的多基因评分。采用多因素logistic回归分析比较ADHD组和对照组的多基因得分，并检测伴有共病性品行障碍的ADHD患者相对于对照组和相对于无共病性品行障碍的ADHD患者的得分是否较高。用线性回归检验与症状评分的关系。从荟萃分析得出，ADHD的多基因风险在独立ADHD组高于对照组。有品行障碍的ADHD患者的多基因评分明显高于无品行障碍的ADHD患者。ADHD多基因评分与共病行为障碍症状有显著相关性。这种关系可以用攻击性项目来解释。常见的遗传变异与多动症有关，特别是在患有共病攻击的个体中。研究结果表明，先前发表的ADHD GWAS荟萃分析与常见变异存在微弱但真实的关联，其支持程度低于全基因组显著性水平。研究结果还强调了这样一个事实，即多动症的攻击性与遗传和临床严重程度有关。
Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.
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影响因子：
5.3
作者：
Franke B;Neale BM;Faraone SV
通讯作者：
Faraone SV
DOI：
10.1016/j.jaac.2010.06.008
发表时间：
2010-09
影响因子：
13.3
作者：
Neale BM;Medland SE;Ripke S;Asherson P;Franke B;Lesch KP;Faraone SV;Nguyen TT;Schäfer H;Holmans P;Daly M;Steinhausen HC;Freitag C;Reif A;Renner TJ;Romanos M;Romanos J;Walitza S;Warnke A;Meyer J;Palmason H;Buitelaar J;Vasquez AA;Lambregts-Rommelse N;Gill M;Anney RJ;Langely K;O'Donovan M;Williams N;Owen M;Thapar A;Kent L;Sergeant J;Roeyers H;Mick E;Biederman J;Doyle A;Smalley S;Loo S;Hakonarson H;Elia J;Todorov A;Miranda A;Mulas F;Ebstein RP;Rothenberger A;Banaschewski T;Oades RD;Sonuga-Barke E;McGough J;Nisenbaum L;Middleton F;Hu X;Nelson S;Psychiatric GWAS Consortium: ADHD Subgroup
通讯作者：
Psychiatric GWAS Consortium: ADHD Subgroup
影响因子：
--
作者：
Langley, Kate;Heron, Jon;Thapar, Anita
通讯作者：
Thapar, Anita
影响因子：
3.9
作者：
Mulligan, Aisling;Anney, Richard J. L.;Gill, Michael
通讯作者：
Gill, Michael
DOI：
10.1016/j.psc.2009.12.004
发表时间：
2010-03
期刊：
The Psychiatric clinics of North America
影响因子：
--
作者：
Faraone SV;Mick E
通讯作者：
Mick E