Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families
Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families
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DOI：
10.1086/422474
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发表时间：
2004-08-01
影响因子：
9.8
通讯作者：
Pulver, AE
中科院分区：
文献类型：
--
作者：
Fallin, MD;Lasseter, VK;Pulver, AE
双相情感障碍（bp）的连锁研究相对较短的历史产生了不一致的结果。受影响的区域很大，但显著性水平较低，效应大小适中。表型和遗传异质性都可能导致无法确定风险位点。BP是一系列明显的家族性情感障碍的一部分，这些障碍是按严重程度组织起来的。异质性的产生可能是因为没有足够的数据来定义频谱边界，而且，一般来说，不太严重的疾病更难以可靠地诊断。为了解决检测BP易感位点的固有复杂性，我们使用了有限的诊断分类和遗传上更均匀的（德系犹太人）家族收集来进行9厘米常染色体全基因组连锁扫描。虽然他们在基因上更同质，但没有数据表明德系犹太人的发病率与其他人群不同。在对41个阿什肯纳兹血统的先证者患有双相情感障碍（BPI）和至少一个其他成员患有双相情感障碍或双相情感障碍（BPII）的基因组扫描中，我们在染色体1、3、11和18上发现了四个提示连锁的区域。后续的基因分型显示，染色体1、3和18上的区域也提示了谱系中受BPI影响的相对对的关联。此外，我们的染色体18q22信号（D18S541和D18S477）与先前的BP发现重叠。这项研究与我们对精神分裂症的伴随研究同时进行，在该研究中，我们使用相同的方法，最近报告了在德系犹太人染色体10q22上存在精神分裂症易感性位点的重要证据。
The relatively short history of linkage studies in bipolar disorders (BPs) has produced inconsistent findings. Implicated regions have been large, with reduced levels of significance and modest effect sizes. Both phenotypic and genetic heterogeneity may have contributed to the failure to define risk loci. BP is part of a spectrum of apparently familial affective disorders, which have been organized by severity. Heterogeneity may arise because of insufficient data to define the spectrum boundaries, and, in general, the less-severe disorders are more difficult to diagnose reliably. To address the inherent complexities in detecting BP susceptibility loci, we have used restricted diagnostic classifications and a genetically more homogeneous (Ashkenazi Jewish) family collection to perform a 9-cM autosomal genomewide linkage scan. Although they are genetically more homogeneous, there are no data to suggest that the rate of illness in the Ashkenazim differs from that in other populations. In a genome scan of 41 Ashkenazi pedigrees with a proband affected with bipolar I disorder (BPI) and at least one other member affected with BPI or bipolar II disorder (BPII), we identified four regions suggestive of linkage on chromosomes 1, 3, 11, and 18. Follow-up genotyping showed that the regions on chromosomes 1, 3, and 18 are also suggestive of linkage in a subset of pedigrees limited to relative pairs affected with BPI. Furthermore, our chromosome 18q22 signal (D18S541 and D18S477) overlaps with previous BP findings. This research is being conducted in parallel with our companion study of schizophrenia, in which, by use of an identical approach, we recently reported significant evidence for a schizophrenia susceptibility locus in the Ashkenazim on chromosome 10q22.