A genome screen of 13 bipolar affective disorder pedigrees provides evidence for susceptibility loci on chromosome 3 as well as chromosomes 9, 13 and 19
A genome screen of 13 bipolar affective disorder pedigrees provides evidence for susceptibility loci on chromosome 3 as well as chromosomes 9, 13 and 19
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DOI：
10.1038/sj.mp.4001114
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发表时间：
2002-01-01
影响因子：
11
通讯作者：
Schofield, PR
中科院分区：
文献类型：
--
作者：
Badenhop, R;Moses, MJ;Schofield, PR
双相情感障碍是一种严重的情绪障碍，困扰着全世界约1%的人口。双胞胎和收养研究表明，遗传因素有助于疾病，虽然许多染色体区域已被牵连，没有易感基因已被确定。我们对来自一个大的双相情感障碍家系的10 cM基因组筛选数据进行了综合分析，我们先前已经报道了与染色体13 q14的连锁（Badenhop et al，2001）和12个家系使用相同的400个微卫星标记进行了独立筛选。这13个家系队列由231个个体组成，包括69个受影响的成员。在异质性条件下，对三种诊断模型和四种遗传模型进行了两点LOD评分分析。对感兴趣区域进行非参数多点分析。两点异质性LOD得分（HLODs）大于1.5，获得了11个标记在整个基因组中，与HLODs大于2.0，这些标记获得。最强的连锁证据是在3q 25 -26，全基因组最大得分为2.49，位于D3 S1279。在3q 25 -26的50 cM区域中的六个标记给出大于1.5的HLOD，其中三个标记产生大于2.0的分数。多点分析表明标记D3 S1569和D3 S1614之间的20 cM峰，最大NPL为2.8（P = 0.004）。其他三个染色体区域也证明了这种连锁关系：9 q31-q33、13 q14和19 q12-q13。染色体3 q和13 q上的区域此前曾与其他躁郁症和精神分裂症研究有关。此外，一些个别家系的LOD评分大于1.5，以前报道的双极易感基因座的染色体18 p11，18 q12，22 q11和8 p22 -23。
Bipolar affective disorder is a severe mood disorder that afflicts approximately 1% of the population worldwide. Twin and adoption studies have indicated that genetic factors contribute to the disorder and while many chromosomal regions have been implicated, no susceptibility genes have been identified. We undertook a combined analysis of 10 cM genome screen data from a single large bipolar affective disorder pedigree, for which we have previously reported linkage to chromosome 13q14 (Badenhop et al, 2001) and 12 pedigrees independently screened using the same 400 microsatellite markers. This 13 pedigree cohort consisted of 231 individuals, including 69 affected members. Two-point LOD score analysis was carried out under heterogeneity for three diagnostic and four genetic models. Non-parametric multipoint analysis was carried out on regions of interest. Two-point heterogeneity LOD scores (HLODs) greater than 1.5 were obtained for 11 markers across the genome, with HLODs greater than 2.0 obtained for four of these markers. The strongest evidence for linkage was at 3q25-26 with a genome-wide maximum score of 2.49 at D3S1279. Six markers across a 50 cM region at 3q25-26 gave HLODs greater than 1.5, with three of these markers producing scores greater than 2.0. Multipoint analysis indicated a 20 cM peak between markers D3S1569 and D3S1614 with a maximum NPL of 2.8 (P = 0.004). Three other chromosomal regions yielded evidence for linkage: 9q31-q33, 13q14 and 19q12-q13. The regions on chromosomes 3q and 13q have previously been implicated in other bipolar and schizophrenia studies. In addition, several individual pedigrees gave LOD scores greater than 1.5 for previously reported bipolar susceptibility loci on chromosomes 18p11, 18q12, 22q11 and 8p22-23.