A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2
A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2
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DOI：
10.1073/pnas.96.10.5604
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发表时间：
1999-05-11
影响因子：
11.1
通讯作者：
Gershon, ES
中科院分区：
文献类型：
--
作者：
Detera-Wadleigh, SD;Badner, JA;Gershon, ES
双相情感障碍是一种严重的精神疾病，其特征是情绪波动和抑郁。家庭，双胞胎，和通过研究表明，一个复杂的遗传病因，可能涉及多个易感基因和环境成分。为了确定染色体位点的脆弱性，我们进行了全基因组扫描约396个人从22个多重家系使用607微卫星标记。多点非参数分析检测到13 q32连锁的最强证据，最大对数比值（lod）为3.5（P = 0.000028）在包括双相I型、双相II型伴重性抑郁症、情感障碍和复发性单相障碍的表型模型下，在1 q31-q32上发现暗示连锁（lod = 2.67; P = 0.00022）和18p11.2（lod = 2.32; P = 0.00054）。我们的基因组扫描确定了其他有趣的区域，7 q31（lod = 2.08; P = 0.00099）和22 q11-q13（lod = 2.1; P = 0.00094），并证实了4p 16，12 q23-q24和21 q22上的报告连锁。通过对整个基因组的全面筛查，我们发现了双相情感障碍的未报告位点，发现了对拟议联系的支持，并获得了双相情感障碍和精神分裂症易感区域重叠的证据。
Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, and adoption studies suggest a complex genetic etiology that may involve multiple susceptibility genes and an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted a genome-wide scan on approximate to 396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence for linkage at 13q32 with a maximal logarithm of odds (lod) score of 3.5 (P = 0.000028) under a phenotype model that included bipolar I, bipolar II with major depression, schizoaffective disorder, and recurrent unipolar disorder, Suggestive linkage was found on 1q31-q32 (lod = 2.67; P = 0.00022) and 18p11.2 (lod = 2.32; P = 0.00054), Recent reports have linked schizophrenia to 13q32 and 18p11.2. Our genome scan identified other interesting regions, 7q31 (lod = 2.08; P = 0.00099) and 22q11-q13 (lod = 2.1; P = 0.00094), and also confirmed reported linkages on 4p16, 12q23-q24, and 21q22. By comprehensive screening of the entire genome, we detected unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar disorder and schizophrenia.