Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12
Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12
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DOI：
10.1038/mp.2008.12
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发表时间：
2008-05-01
影响因子：
11
通讯作者：
Lesch, K. P.
中科院分区：
文献类型：
--
作者：
Romanos, M.;Freitag, C.;Lesch, K. P.
先前的全基因组连锁研究应用了受影响的同胞对设计；其中一项研究了基因分离株的扩展谱系。这里展示了使用类似于 50K 单核苷酸多态性 (SNP) 标记的基于阵列的基因分型对注意力缺陷/多动症 (ADHD) 进行全基因组高密度连锁扫描的结果。我们调查了八个德国血统的扩展谱系，这些谱系不相关，不属于遗传分离的一部分，并根据临床转诊进行确定。进行了两项最大化 LOD 评分 (MOD) 的参数分析和针对广义和狭义表型方法的非参数分析。所有家族的新连锁位点均在 2q35、5q13.1、6q22-23 和 14q12 处检测到，在各个家族内则在 18q11.2-12.3 处检测到。所有家族中 7q21.11、9q22 和 16q24.1 的进一步连锁区域，以及个别家族中 1q25.1、1q25.3、9q31.1-33.1、9q33、12p13.33、15q11.2-13.3 和 16p12.3-12.2 的进一步连锁区域重复了之前的发现。高分辨率连锁图谱指出了几个新的候选基因，其特征是在大脑中密集表达以及对疾病相关突触传递的潜在影响。尽管 ADHD 的病因学复杂，涉及多因素，但我们的研究为不同人群中常见的基因效应提供了进一步的证据。
Previous genome-wide linkage studies applied the affected sib-pair design; one investigated extended pedigrees of a genetic isolate. Here, results of a genome-wide high-density linkage scan of attention-deficit/hyperactivity disorder (ADHD) using an array-based genotyping of similar to 50K single nucleotide polymorphism (SNPs) markers are presented. We investigated eight extended pedigrees of German origin that were non-related, not part of a genetic isolate and ascertained on the basis of clinical referral. Two parametric analyses maximizing LOD scores (MOD) and a non-parametric analysis for both a broad and a narrow phenotype approach were conducted. Novel linkage loci across all families were detected at 2q35, 5q13.1, 6q22-23 and 14q12, within individual families at 18q11.2-12.3. Further linkage regions at 7q21.11, 9q22 and 16q24.1 in all families, and at 1q25.1, 1q25.3, 9q31.1-33.1, 9q33, 12p13.33, 15q11.2-13.3 and 16p12.3-12.2 in individual families replicate previous findings. High-resolution linkage mapping points to several novel candidate genes characterized by dense expression in the brain and potential impact on disorder-relevant synaptic transmission. Our study provides further evidence for common gene effects throughout different populations despite the complex multifactorial etiology of ADHD.