A genomewide linkage study of age at onset in schizophrenia
A genomewide linkage study of age at onset in schizophrenia
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DOI：
10.1002/ajmg.1404
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发表时间：
2001-07-08
期刊：
影响因子：
--
通讯作者：
Owen, MJ
中科院分区：
文献类型：
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作者：
Cardno, AG;Holmans, PA;Owen, MJ
有强有力的证据表明，基因对精神分裂症发病年龄有影响，这可能涉及精神分裂症的易感性位点和独立于疾病风险的修饰位点。我们在94对患有DSM-TV精神分裂症或分裂情感性障碍的受影响兄弟姐妹样本中寻找影响精神分裂症发病年龄和首次精神接触年龄在45岁或以下的基因座的关联证据。个体在整个基因组中以大约20 cM的间隔进行229个微卫星标记的基因分型。使用MAPMAKER/SIBS进行定量最大似然多点连锁分析，寻找与发病年龄有关的基因座，并进行非参数多点分析。通过模拟研究评估连锁结果的全基因组意义。有6个最大似是性LOD评分峰值为1.5或更高，最高的是染色体17q (LOD = 2.54；全基因组P = 0.27)，这满足了Lander和Kruglyak [1995: Nat Genet 11:41 -247]的暗示连锁标准，即每次基因组扫描预计发生一次或更少（0.3次）。然而，这一发现应该谨慎对待，因为LOD评分似乎几乎完全由一个标记（D17S787）的ibd共享模式所决定，几乎没有证据表明在侧翼标记上存在连锁。所有连锁结果均不具有全基因组的统计学意义，但13q染色体上的LOD评分峰值（LOD = 1.68）与Blouin等[1998:Nat Genet 20:70-73]研究中显示的分类精神分裂症连锁证据最多的区域重合。(C) 2001 Wiley-Liss, Inc。
There is strong evidence for a genetic contribution to age at onset of schizophrenia, which probably involves both susceptibility loci for schizophrenia and modifying loci acting independent of disease risk. We sought evidence of linkage to loci that influence age at onset of schizophrenia in a sample of 94 affected sibling pairs with DSM-TV schizophrenia or schizoaffective disorder, and age at first psychiatric contact of 45 years or less, Individuals were genotyped for 229 microsatellite markers spaced at approximately 20 cM intervals throughout the genome. Loci contributing to age at onset were sought by a quantitative maximum-likelihood multipoint linkage analysis using MAPMAKER/SIBS, A nonparametric multipoint analysis was also performed. The genomewide significance of linkage results was assessed by simulation studies. There were six maximum-likelihood LOD score peaks of 1.5 or greater, the highest being on chromosome 17q (LOD = 2.54; genomewide P = 0.27), This fulfils Lander and Kruglyak's [1995: Nat Genet 11:241-247] criteria for suggestive linkage in that it would be expected to occur once or less (0.3 times) per genome scan. However, this finding should be treated with caution because the LOD score appeared to be almost solely accounted for by the pattern of ibd sharing at one marker (D17S787), with virtually no evidence of linkage over flanking markers. None of the linkage results achieved genomewide statistical significance, but the LOD score peak on chromosome 13q (LOD = 1.68) coincided with the region showing maximum evidence for linkage in the study by Blouin et al, [1998: Nat Genet 20:70-73] of categorical schizophrenia. (C) 2001 Wiley-Liss, Inc.