A heterogeneity-based genome search meta-analysis for autism-spectrum disorders
A heterogeneity-based genome search meta-analysis for autism-spectrum disorders
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基于异质性的自闭症谱系障碍基因组搜索荟萃分析
DOI：
10.1038/sj.mp.4001750
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发表时间：
2006
影响因子：
11
通讯作者：
J. Ioannidis
中科院分区：
文献类型：
--
作者：
T. Trikalinos;T. Trikalinos;A. Karvouni;E. Zintzaras;T. Ylisaukko‐oja;L. Peltonen;I. Järvelä;I. Järvelä;J. Ioannidis;J. Ioannidis;J. Ioannidis
自闭症和自闭症谱系障碍表现出高遗传性，尽管特定的易感基因仍然在很大程度上难以捉摸。我们进行了基于异质性的基因组搜索荟萃分析（HEGESMA）的9个基因组扫描自闭症或自闭症谱系障碍。将每个基因组扫描分离在30 cM箱中，并对来自每个箱的最大连锁统计进行排序。通过Monte Carlo检验获得每个箱的平均秩和扫描间异质性（平均秩的不相似性）的显著性。对于自闭症，来自771个受影响的同胞对的数据通过六个独立的基因组扫描进行合成。区域7 q22-q32在加权和未加权分析中均达到全基因组显著性，有证据表明扫描间异质性显著较低。侧翼染色体区域7 q32-qter达到了暗示意义的不太严格的阈值，没有证据表明扫描间异质性较低。对于自闭症谱系障碍（来自五次单独扫描的634个受影响的同胞），没有染色体区域达到全基因组意义。然而，在加权分析中，染色体区域17p11.2-q12和10 p12-q11.1达到了提示意义。有证据表明前一区域的扫描间异质性显著较高。荟萃分析表明，7 q22-q32区域应该进一步审查自闭症易感基因，而自闭症谱系障碍似乎在扫描中具有相当不同的连锁信号，这可能表明亚综合征和亚群之间的遗传异质性。
Autism and autism-spectrum disorders exhibit high heritability, although specific susceptibility genes still remain largely elusive. We performed a heterogeneity-based genome search meta-analysis (HEGESMA) of nine genome scans on autism or autism-spectrum disorders. Each genome scan was separated in 30 cM bins and the maximum linkage statistic from each bin was ranked. Significance for each bin's average rank and for between-scan heterogeneity (dis-similarity in the average ranks) was obtained through Monte Carlo tests. For autism, data from 771 affected sibpairs were synthesized across six separate genome scans. Region 7q22–q32 reached genome-wide significance both in weighted and unweighted analyses, with evidence for significantly low between-scan heterogeneity. The flanking chromosomal region 7q32-qter reached the less stringent threshold of suggestive significance, with no evidence for low between-scan heterogeneity. For autism-spectrum disorders (634 affected sibpairs from five separate scans), no chromosomal region reached genome-wide significance. However, suggestive significance was reached for the chromosomal regions 17p11.2–q12 and 10p12–q11.1 in weighted analyses. There was evidence for significantly high between-scan heterogeneity for the former region. The meta-analysis suggests that the 7q22–q32 region should be further scrutinized for autism susceptibility genes, while autism-spectrum disorders seem to have quite diverse linkage signals across scans, possibly suggesting genetic heterogeneity across subsyndromes and subpopulations.
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自闭症常染色体基因组筛查。
DOI：
--
发表时间：
2001
期刊：
American journal of medical genetics
影响因子：
--
作者：
CollaborativeLinkageStudyofAutism
通讯作者：
CollaborativeLinkageStudyofAutism
影响因子：
9.8
作者：
Risch, N;Spiker, D;Myers, RM
通讯作者：
Myers, RM
影响因子：
9.8
作者：
Auranen, M;Vanhala, R;Järvelä, I
通讯作者：
Järvelä, I
影响因子：
9.8
作者：
Cantor, RM;Kono, N;Geschwind, DH
通讯作者：
Geschwind, DH