Brookes K J, Neale B, Xu X, Thapar A, Gill M, Langley K, Hawi Z, Mill J, Taylor E, Franke B, Chen W, Ebstein R, Buitelaar J, Banaschewski T, Sonuga-Barke E, Eisenberg J, Manor I, Miranda A, Oades R D, Roeyers H, Rothenberger A, Sergeant J, Steinhausen H C, Faraone S V, Asherson P
MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):94-9. doi: 10.1002/ajmg.b.30562.
Season of birth (SOB) has been associated with attention deficit hyperactivity disorder (ADHD) in two existing studies. One further study reported an interaction between SOB and genotypes of the dopamine D4 receptor (DRD4) gene. It is important that these findings are further investigated to confirm or refute the findings. In this study, we investigated the SOB association with ADHD in four independent samples collected for molecular genetic studies of ADHD and found a small but significant increase in summer births compared to a large population control dataset. We also observed a significant association with the 7-repeat allele of the DRD4 gene variable number tandem repeat polymorphism in exon three with probands born in the winter season, with no significant differential transmission of this allele between summer and winter seasons. Preferential transmission of the 2-repeat allele to ADHD probands occurred in those who were born during the summer season, but did not surpass significance for association, even though the difference in transmission between the two seasons was nominally significant. However, following adjustment for multiple testing of alleles none of the SOB effects remained significant. We conclude that the DRD4 7-repeat allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD. Our findings suggest that we can refute a possible effect of SOB for ADHD.
在两项现有研究中，出生季节（SOB）与注意力缺陷多动障碍（ADHD）相关。另一项研究报告了SOB与多巴胺D4受体（DRD4）基因的基因型之间存在相互作用。进一步研究这些发现以证实或反驳这些结果很重要。在本研究中，我们在为ADHD分子遗传学研究收集的四个独立样本中调查了SOB与ADHD的关联，发现与大量人群对照数据集相比，夏季出生的人数有小幅但显著的增加。我们还观察到，外显子3中DRD4基因可变数目串联重复多态性的7重复等位基因与冬季出生的先证者存在显著关联，该等位基因在夏季和冬季之间没有显著的差异传递。2重复等位基因向夏季出生的ADHD先证者的优先传递发生了，但即使两个季节之间的传递差异在名义上是显著的，也没有超过关联的显著性。然而，在对等位基因进行多重检验校正后，SOB的所有效应均不再显著。我们得出结论，DRD4 7重复等位基因与ADHD相关，但SOB与ADHD风险增加没有关联或相互作用。我们的研究结果表明，我们可以反驳SOB对ADHD可能产生的影响。
