Cognitive functioning in affected sibling pairs with ADHD: familial clustering and dopamine genes.
Cognitive functioning in affected sibling pairs with ADHD: familial clustering and dopamine genes.
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DOI：
10.1111/j.1469-7610.2008.01928.x
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发表时间：
2008-09
期刊：
影响因子：
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通讯作者：
S. Loo;Erika Carpenter Rich;Janeen Ishii;J. McGough;J. McCracken;S. Nelson;S. Smalley
中科院分区：
文献类型：
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作者：
S. Loo;Erika Carpenter Rich;Janeen Ishii;J. McGough;J. McCracken;S. Nelson;S. Smalley
背景：本文探讨了注意力缺陷多动障碍（ADHD）中作为潜在内表型的认知测量的家族性和候选基因关联。样本由540名参与者组成，年龄在6到18岁之间，他们被诊断患有ADHD，来自251个家庭，这些家庭被招募用于更大的ADHD遗传研究。所有的家庭成员都接受了精神病学的采访，孩子们被管理了大量的认知任务。受试者的基因分型为几个多巴胺能候选基因（DAT 1，DRD 4和DRD 5）。结果：智力、工作记忆和定势转换的测量结果具有最高的同胞相关性，并表现出显着的家族聚集性。多巴胺受体D4（DRD 4）基因的7-重复等位基因与智力、颜色命名、干扰控制和工作记忆的测量结果相关。与DAT 1和DRD 5无显著相关性。结论：同胞相关性、家族聚集性和候选基因关联性为言语工作记忆作为ADHD的候选内表型提供了强有力的支持。更复杂的模型，更大的样本量，与认知功能的遗传关联，鼓励未来的研究。
BACKGROUND This paper examines familiality and candidate gene associations of cognitive measures as potential endophenotypes in attention-deficit/hyperactivity disorder (ADHD). METHODS The sample consists of 540 participants, aged 6 to 18, who were diagnosed with ADHD from 251 families recruited for a larger genetic study of ADHD. All members of the family underwent psychiatric interviews and children were administered a large battery of cognitive tasks. Subjects were genotyped for several dopaminergic candidate genes (DAT1, DRD4, and DRD5). RESULTS Performance on measures of intelligence, working memory, and set-shifting had the highest sibling correlations and exhibited significant familial clustering. The 7-repeat allele of the dopamine receptor D4 (DRD4) gene was associated with poor performance on measures of intelligence, color naming, interference control, and working memory. There were no significant associations with DAT1 and DRD5. CONCLUSIONS Sibling correlations, familial clustering and candidate gene associations provide strong support for verbal working memory as a candidate endophenotype for ADHD. More complex models of, and larger sample sizes for, genetic association with cognitive functions are encouraged for future study.