Zhou Kaixin, Asherson Philip, Sham Pak, Franke Barbara, Anney Richard J L, Buitelaar Jan, Ebstein Richard, Gill Michael, Brookes Keeley, Buschgens Cathelijne, Campbell Desmond, Chen Wai, Christiansen Hanna, Fliers Ellen, Gabriëls Isabel, Johansson Lena, Marco Rafaela, Mulas Fernando, Müller Ueli, Mulligan Aisling, Neale Benjamin M, Rijsdijk Fruhling, Rommelse Nanda, Uebel Henrik, Psychogiou Lamprini, Xu Xiaohui, Banaschewski Tobias, Sonuga-Barke Edmund, Eisenberg Jacques, Manor Iris, Miranda Ana, Oades Robert D, Roeyers Herbert, Rothenberger Aribert, Sergeant Joseph, Steinhausen Hans-Christoph, Taylor Eric, Thompson Margaret, Faraone Stephen V
MRC Social Genetic Developmental and Psychiatry Centre, King's College London, London, UK.
Biol Psychiatry. 2008 Oct 1;64(7):571-6. doi: 10.1016/j.biopsych.2008.02.024. Epub 2008 Apr 24.
Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL).
A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collected and standardized according to a population sample of 8000 children to reflect the developmental nature and gender prevalence difference of ADHD. Univariate linkage test was performed on both traits and their mean score.
A significant common linkage locus was found at chromosome 1p36 with a locus-specific heritability of 5.1% and a genomewide empirical p < .04. Setting-specific suggestive linkage signals were also found: logarithm of odds (LOD) = 2.2 at 9p23 for home trait and LOD = 2.6 at 11q21 for school trait.
These results indicate that given large samples with proper phenotypic measures, searching for ADHD genes with a QTL strategy is an important alternative to using the clinical diagnosis. The fact that our linkage region 1p36 overlaps with the dyslexia QTL DYX8 further suggests it is potentially a pleiotropic locus for ADHD and dyslexia.
既往注意力缺陷多动障碍(ADHD)连锁扫描取得的成功有限,这些扫描均旨在定位二分法表型背后的基因。国际多中心ADHD遗传学(IMAGE)项目进行了一项全基因组连锁扫描,专门用于定位ADHD数量性状基因座(QTL)。
对一组1094个经过挑选的白种人ADHD核心家庭在一个高度准确且信息丰富的单核苷酸多态性(SNP)面板上进行基因分型。收集了两项衡量儿童在家和学校环境中症状的数量性状,并根据8000名儿童的人群样本进行标准化,以反映ADHD的发育本质和性别患病率差异。对这两项性状及其平均得分进行单变量连锁测试。
在1号染色体p36区域发现了一个显著的共同连锁基因座,位点特异性遗传度为5.1%,全基因组经验性p<0.04。还发现了特定环境下的提示性连锁信号:在家中性状方面,9号染色体p23区域的优势对数(LOD)=2.2;在学校性状方面,11号染色体q21区域的LOD=2.6。
这些结果表明,在有适当表型测量的大样本情况下,采用QTL策略寻找ADHD基因是替代临床诊断的重要方法。我们的连锁区域1p36与阅读障碍QTL DYX8重叠这一事实进一步表明,它可能是ADHD和阅读障碍的一个多效性基因座。