Lasky-Su Jessica, Banaschewski Tobias, Buitelaar Jan, Franke Barbara, Brookes Keeley, Sonuga-Barke Edmund, Ebstein Richard, Eisenberg Jacques, Gill Michael, Manor Iris, Miranda Ana, Mulas Fernando, Oades Robert D, Roeyers Herbert, Rothenberger Aribert, Sergeant Joseph, Steinhausen Hans-Christoph, Taylor Eric, Zhou Kaixin, Thompson Margaret, Asherson Philip, Faraone Stephen V
Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Biol Psychiatry. 2007 Nov 1;62(9):985-90. doi: 10.1016/j.biopsych.2007.03.006. Epub 2007 Jun 8.
Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals.
Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4.
One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result.
This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.
先前的研究发现，多巴胺D4受体（DRD4）启动子区域的单核苷酸多态性（SNP）与注意力缺陷多动障碍（ADHD）症状所衍生的统计学表型之间存在关联。我们试图通过在独立的ADHD个体样本中使用相同的方法来重复这一发现。
对642个家庭的2631名个体的DRD4及其周围的四个SNP进行基因分型。我们通过对九个注意力不集中症状和九个多动冲动症状进行加权，在每个SNP处开发了一个定量表型。选择这些权重以最大化每个SNP的遗传力。一旦在每个SNP处生成定量表型，就使用PBAT中实施的筛选程序来选择和测试五个具有最大检测DRD4关联能力的SNP/遗传模型组合。
四个SNP中的一个与ADHD症状所产生的定量表型相关（校正p值 = 0.02）。每个ADHD症状与定量表型之间的相关性排序表明，多动冲动症状与该表型的相关性更强；然而，纳入注意力不集中症状对于获得显著结果是必要的。
本研究通过鉴定rs7124601与ADHD症状所产生的定量性状之间的关联，部分重复了先前的发现。rs7124601与先前鉴定的SNP处于连锁不平衡（LD）状态。与先前的研究相比，这一发现表明多动冲动症状和注意力不集中症状在这种关联中都很重要。
