DSM-IV Combined Type ADHD Shows Familial Association With Sibling Trait Scores: A Sampling Strategy For QTL Linkage
DSM-IV Combined Type ADHD Shows Familial Association With Sibling Trait Scores: A Sampling Strategy For QTL Linkage
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DOI：
10.1002/ajmg.b.30672
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发表时间：
2008-12-05
影响因子：
2.8
通讯作者：
Asherson, Philip
中科院分区：
文献类型：
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作者：
Chen, Wai;Zhou, Kaixin;Asherson, Philip
注意缺陷多动障碍（ADHD）是一种以注意力不集中、多动和冲动为特征的临床症状。分子遗传学研究已经成功地确定了与多动症相关的遗传变异，特别是与DSM-IV中注意力不集中和合并亚型相关的遗传变异。尽管调查个体差异的双胞胎研究表明，ADHD的遗传倾向在整个人群中持续分布，强调了定量维度方法的适用性，但用于连锁和关联定位的数量性状位点（QTL）方法尚未广泛应用于ADHD研究。为了研究QTL方法的适宜性，我们在1135名未选择表型的兄弟姐妹中测试了894名研究诊断为DSM-IV ADHD联合型和连续性状测量的先证之间的家族关联。ADHD合并亚型的兄弟姐妹复发率为12.7%，兄弟姐妹复发风险比（lambda(sib)）为9.0。估计的兄弟姐妹相关性约为0.2-0.3，与从总体双胞胎样本中对异卵双胞胎的分析估计的结果相似。我们进一步表明，在ADHD先证中，兄弟姐妹患ADHD的风险没有阈值效应；受影响和未受影响的兄弟姐妹都与ADRD特征得分有关。总之，这些数据证实了ADHD QTL定位的主要要求，表明狭义的DSM-IV组合型先证与兄弟姐妹之间的维度ADHD症状评分存在家族关联。(c) 2008 Wiley-Liss, Inc。
Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches. To investigate the appropriateness: of QTL approaches, we tested the familial association between 894 probands with a research diagnosis of DSM-IV ADHD combined type and continuous trait measures among 1,135 of their siblings unselected for phenotype. The sibling recurrence rate for ADHD combined subtype was 12.7%, yielding a sibling recurrence risk ratio (lambda(sib)) of 9.0. Estimated sibling correlations around 0.2-0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples. We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD probands; and that both affected and unaffected siblings contributed to the association with ADRD trait scores. In conclusion, these data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM-IV combined type probands show familial association with dimensional ADHD symptom scores amongst their siblings. (c) 2008 Wiley-Liss, Inc.