Douglas Mental Health University Institute, McGill University, Verdun, QC, Canada.
J Child Psychol Psychiatry. 2012 Aug;53(8):892-902. doi: 10.1111/j.1469-7610.2012.02551.x. Epub 2012 Apr 7.
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder, complex both in etiology and clinical expression. Both genetic and environmental factors have been implicated, and it has been suggested that gene-environment interactions may play a pivotal role in the disorder. Recently, a significant association was reported between ADHD and LPHN3 (which codes for latrophilin 3), and replicated in independent samples.
We have examined the association between tag single nucleotide polymorphisms (SNPs) in LPHN3 within the region previously implicated in ADHD. Family based association tests (FBAT) were conducted (n = 380 families) with the categorical diagnosis of ADHD, behavioral and cognitive phenotypes related to ADHD, and response to treatment (given a fixed dose of methylphenidate, 0.5 mg/day). Stratified FBAT analyses, based on maternal smoking and stress during pregnancy, was conducted.
Whereas limited association was observed in the total sample, highly significant interaction between four LPHN3 tag SNPs (rs6551665, rs1947274, rs6858066, rs2345039) and maternal stress during pregnancy was noted. Analysis conducted in the sub-group of mothers exposed to minimal stress during pregnancy showed significant associations with ADHD, behavioral and cognitive dimensions related to ADHD, as well as treatment response. Although extensive association was observed with the candidate SNPs, the findings are partially inconsistent with previously published results with the opposite alleles over-transmitted in these studies.
These results provide evidence for the interaction between a genetic and environmental factor independently shown to be associated with ADHD. If confirmed in independent large studies, they may present a step forward in unraveling the complex etiology of ADHD.
注意缺陷多动障碍（ADHD）是一种异质性行为障碍，其病因和临床表现都很复杂。遗传和环境因素都有涉及，并且有人提出基因-环境相互作用可能在该疾病中起关键作用。最近，有研究报道 ADHD 与 LPHN3 之间存在显著关联，该研究在独立样本中得到了复制。
我们已经研究了先前与 ADHD 相关的区域内 LPHN3 的标签单核苷酸多态性（SNP）与 ADHD、与 ADHD 相关的行为和认知表型以及对治疗的反应（给予固定剂量的哌甲酯，0.5mg/天）之间的关联。根据母亲怀孕期间的吸烟和压力情况进行了基于分层的 FBAT 分析。
虽然在总样本中观察到有限的关联，但在 LPHN3 的四个标签 SNP（rs6551665、rs1947274、rs6858066、rs2345039）与母亲怀孕期间的压力之间观察到了高度显著的相互作用。在暴露于最小压力的母亲亚组中进行的分析显示与 ADHD、与 ADHD 相关的行为和认知维度以及治疗反应显著相关。尽管候选 SNPs 存在广泛的关联，但这些发现与先前研究中相反等位基因过度传递的结果部分不一致。
这些结果为遗传和环境因素之间的相互作用提供了证据，这些因素都已被证明与 ADHD 相关。如果在独立的大型研究中得到证实，它们可能是揭示 ADHD 复杂病因的一个重要进展。
