Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22
Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22
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DOI：
10.1086/378158
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发表时间：
2003-09-01
影响因子：
9.8
通讯作者：
Pulver, AE
中科院分区：
文献类型：
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作者：
Fallin, MD;Lasseter, VK;Pulver, AE
以前的精神分裂症连锁研究一直令人沮丧，由于不一致的结果和微弱的信号。遗传异质性被认为是造成这种不一致的主要原因之一。我们已经进行了10厘米的常染色体全基因组连锁扫描精神分裂症的易感区域，使用29个多重家庭的德系犹太血统。虽然没有证据表明德系犹太人的精神分裂症发病率与其他人群不同，但我们将重点放在这一人群上，希望减少家族间的遗传异质性，并增加任何特定位点的可检测效应。我们进行了等位基因共享和参数连锁分析，如Genehunter 2.0版中所实施的。我们最强的信号是在染色体10q22.3（D10 S1686），非参数连锁评分（NPL）为3.35（全基因组经验）和显性异质性LOD评分（HLOD）为3.14。其他6个区域的NPL评分>2.00（染色体1p32.2、4q34.3、6p21.31、7p15.2、15q11.2和21q21.2）。在染色体10 q区域中使用另外23个标记进行随访后，我们的峰值NPL评分增加到4.27（D10 S1774;经验P = .00002），性状基因座位置的95%置信区间为12.2Mb（D10 S1677至D10 S1753）。我们发现这些结果令人鼓舞的德系犹太人家庭中的精神分裂症的研究，并建议进一步的连锁和关联研究，在这个染色体10 q区域。
Previous linkage studies in schizophrenia have been discouraging due to inconsistent findings and weak signals. Genetic heterogeneity has been cited as one of the primary culprits for such inconsistencies. We have performed a 10-cM autosomal genomewide linkage scan for schizophrenia susceptibility regions, using 29 multiplex families of Ashkenazi Jewish descent. Although there is no evidence that the rate of schizophrenia among the Ashkenazim differs from that in other populations, we have focused on this population in hopes of reducing genetic heterogeneity among families and increasing the detectable effects of any particular locus. We pursued both allele-sharing and parametric linkage analyses as implemented in Genehunter, version 2.0. Our strongest signal was achieved at chromosome 10q22.3 (D10S1686), with a nonparametric linkage score (NPL) of 3.35 (genomewide empirical) and a dominant heterogeneity LOD score ( HLOD) of 3.14. Six other regions gave NPL scores >2.00 (on chromosomes 1p32.2, 4q34.3, 6p21.31, 7p15.2, 15q11.2, and 21q21.2). Upon follow- up with an additional 23 markers in the chromosome 10q region, our peak NPL score increased to 4.27 (D10S1774; empirical P = .00002), with a 95% confidence interval of 12.2 Mb for the location of the trait locus (D10S1677 to D10S1753). We find these results encouraging for the study of schizophrenia among Ashkenazi families and suggest further linkage and association studies in this chromosome 10q region.