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
复制标题
DOI：
10.1038/sj.mp.4001025
复制
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, RF;Moses, MJ;Schofield, PR
双相情感障碍是一种严重的情绪障碍，困扰着全球约1%的人口。双胞胎和领养研究表明，遗传因素导致了这种疾病，虽然许多染色体区域都有牵连，但还没有发现易感基因。我们对一个大型双相情感障碍家系的10 cM基因组筛查数据进行了联合分析，此前我们曾报道该家系与染色体13q14连锁(Bdenhop等人，2001年)，并使用相同的400个微卫星标记对12个家系进行了独立筛查。这个13个家系的队列由231人组成，其中包括69名受影响的成员。对3个诊断模型和4个遗传模型进行了异质性下的两点LOD评分分析。对感兴趣区进行非参数多点分析。全基因组的11个标记获得了大于1.5的两点异质性LOD分数(HLOD)，其中4个标记获得了大于2.0的HLOD。连锁的最有力证据是3q25-26，D3S1279的全基因组最高得分为2.49。在3q25-26的50 cM区域内，有6个标记的HLOD大于1.5，其中3个标记的HLOD大于2.0。多点分析显示，在标记D3S1569和D3S1614之间有一个20 cM的峰值，最大ILI2.8(P=0.004)。另外三个染色体区域：9q31-q33、13q14和19q12-q13也提供了连锁的证据。染色体3q和13q上的区域之前曾被认为与其他双相情感障碍和精神分裂症的研究有关。此外，一些个体家系的双相易感基因座在染色体18p11、18q12、22q11和8p22-23上的LOD得分大于1.5。
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 Ill 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.