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多巴胺受体D1基因(DRD1)与因阅读问题而入选的家庭中的注意力不集中症状的关联。

Association of the dopamine receptor D1 gene, DRD1, with inattention symptoms in families selected for reading problems.

作者信息

Luca P, Laurin N, Misener V L, Wigg K G, Anderson B, Cate-Carter T, Tannock R, Humphries T, Lovett M W, Barr C L

机构信息

Cell and Molecular Biology Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.

出版信息

Mol Psychiatry. 2007 Aug;12(8):776-85. doi: 10.1038/sj.mp.4001972. Epub 2007 Feb 20.

Abstract

Twin studies have provided evidence for shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) and specific reading disabilities (RD), with this overlap being highest for the inattentive symptom dimension of ADHD. Previously, we found evidence for association of the dopamine receptor D1 gene (DRD1) with ADHD, and with the inattentive symptom dimension in particular. This, combined with evidence for working memory (WM) deficits in individuals with RD or ADHD, and the importance of D1 receptors in attentional processes and WM function, suggests that DRD1 may be a common genetic influence underlying both disorders. Here, in a study of 232 families ascertained through probands with reading problems, we tested for association of the DRD1 gene with RD, as a categorical trait, and with quantitative measures of key reading component skills, WM ability, and inattentive symptoms. Although no associations were found with RD, or with reading component skills or verbal WM, we found evidence for association with inattentive behaviour. Specifically, DRD1 Haplotype 3, the haplotype previously found to be associated with inattentive symptoms in ADHD, is also associated with parent- and teacher-reported symptoms of inattention in this sample selected for reading problems (P=0.023 and 0.004, respectively). Together, the replicated finding of Haplotype 3 association with inattentive symptoms in two independent study samples strongly supports a role for DRD1 in attentional ability. Furthermore, the association of DRD1 with inattention, but not with RD, or the other reading and reading-related phenotypes analysed, suggests that DRD1 contributes uniquely to inattention, without overlap for reading ability.

摘要

双胞胎研究为注意力缺陷/多动障碍(ADHD)和特定阅读障碍(RD)之间存在共同的遗传影响提供了证据,ADHD的注意力不集中症状维度与RD的这种重叠最为明显。此前,我们发现多巴胺受体D1基因(DRD1)与ADHD有关,尤其是与注意力不集中症状维度有关。这一点,再加上有证据表明患有RD或ADHD的个体存在工作记忆(WM)缺陷,以及D1受体在注意力过程和WM功能中的重要性,表明DRD1可能是这两种障碍共同的遗传影响因素。在此,在一项对232个通过有阅读问题的先证者确定的家庭进行的研究中,我们测试了DRD1基因与作为分类性状的RD以及关键阅读组成技能、WM能力和注意力不集中症状的量化指标之间的关联。尽管未发现与RD、阅读组成技能或言语WM有关联,但我们发现了与注意力不集中行为有关联的证据。具体而言,DRD1单倍型3,即先前发现与ADHD注意力不集中症状相关的单倍型,在这个因阅读问题而选取的样本中也与家长和教师报告的注意力不集中症状相关(分别为P = 0.023和0.004)。单倍型3与注意力不集中症状在两个独立研究样本中的重复关联结果有力地支持了DRD1在注意力能力方面的作用。此外,DRD1与注意力不集中有关,但与RD或其他所分析的阅读及与阅读相关的表型无关,这表明DRD1对注意力不集中有独特的影响,与阅读能力没有重叠。

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