Genome-wide scan of bipolar disorder and investigation of population stratification effects on linkage: Support for susceptibility loci at 4q21, 7q36, 9p21, 12q24, 14q24, and 16p13
Genome-wide scan of bipolar disorder and investigation of population stratification effects on linkage: Support for susceptibility loci at 4q21, 7q36, 9p21, 12q24, 14q24, and 16p13
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DOI：
10.1002/ajmg.b.30524
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发表时间：
2007-09-05
影响因子：
2.8
通讯作者：
McKeon, P.
中科院分区：
文献类型：
--
作者：
Cassidy, F.;Zhao, C.;McKeon, P.
双相情感障碍（BPD）是一种复杂的遗传性疾病，具有抑郁和躁狂的循环症状。尽管这种精神疾病极其复杂，但定位导致该疾病易感性的基因的尝试已经取得了一些成功。包括 4p16、12q24、18p11、18q22 和 21q21 在内的染色体区域已在不同人群中反复与 BPD 相关。在这里，我们展示了爱尔兰人群中与 BPD 关联的全基因组扫描结果。我们最显着的结果是在 14q24，其在 D14S588 标记处产生的非参数 LOD (NPL) 得分为 3.27，在狭窄（仅限双相 I 型）情感模型下名义 P 值为 0.0006。我们之前报告了本分析中测试的一个家族子集中与 14q22-24 的连锁。我们还获得了 4q21、9p21、12q24 和 16p13 染色体区域连锁的提示性证据，这些区域以前都与 BPD 相关。此外，我们报告了一种新的连锁分析方法，即结构引导连锁分析（SGLA），该方法旨在减少遗传异质性并提高检测连锁的能力。该技术的应用产生了更重要的证据，证明 BPD 与三个区域（包括 16p13）的关联，该基因座已反复与许多精神疾病相关。 (c) 2007 年 Wiley-Liss, Inc.
Bipolar disorder (BPD) is a complex genetic disorder with cycling symptoms of depression and mania. Despite the extreme complexity of this psychiatric disorder, attempts to localize genes which confer vulnerability to the disorder have had some success. Chromosomal regions including 4p16,12q24,18p11, 18q22, and 21q21 have been repeatedly linked to BPD in different populations. Here we present the results of a whole genome scan for linkage to BPD in an Irish population. Our most significant result was at 14q24 which yielded a non-parametric LOD (NPL) score of 3.27 at the D14S588 marker with a nominal P-value of 0.0006 under a narrow (bipolar type I only) model of affection. We previously reported linkage to 14q22-24 in a subset of the families tested in this analysis. We also obtained suggestive evidence for linkage at 4q21, 9p21, 12q24, and 16p13, chromosomal regions that have all been previously linked to BPD. Additionally, we report on a novel approach to linkage analysis, STRUCTURE-Guided Linkage Analysis (SGLA), which is designed to reduce genetic heterogeneity and increase the power to detect linkage. Application of this technique resulted in more highly significant evidence for linkage of BPD to three regions including 16p13, a locus that has been repeatedly linked to numerous psychiatric disorders. (c) 2007 Wiley-Liss, Inc.