Meta-analysis of 32 genome-wide linkage studies of schizophrenia.
Meta-analysis of 32 genome-wide linkage studies of schizophrenia.
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DOI：
10.1038/mp.2008.135
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发表时间：
2009-08
影响因子：
11
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中科院分区：
文献类型：
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对32项独立的全基因组连锁扫描分析进行了基因组扫描荟萃分析（GSMA），其中包括3255个家系，7413例精神分裂症（SCZ）或相关疾病的基因分型病例。初级GSMA将常染色体分为120个bin，根据每个bin中最积极的连锁结果对每个研究中的bin进行排序，对研究中每个bin的这些排名（根据研究规模加权）进行汇总，并通过模拟确定给定的汇总排名（PSR）的经验概率。在5q染色体（142-168 Mb）和2q染色体（103-134 Mb）两个单箱中观察到提示性的连锁证据。当箱边界移到先前箱的中间时，在染色体2q （119-152 Mb）上检测到全基因组连锁证据。初步分析符合“总体”全基因组显著性的经验标准，表明10个箱子中的部分或全部可能包含与SCZ相关的位点，包括染色体1、2q、3q、4q、5q、8p和10q的区域。在对22份欧洲血统样本的二次分析中，在染色体8p （16-33 Mb）上观察到连锁的暗示性证据。虽然较新的全基因组关联方法在检测单个常见DNA序列变异的弱关联方面具有更大的能力，但连锁分析可以检测家族中分离的多种遗传效应，包括一个位点内的多个罕见变异或同一区域的几个弱相关位点。因此，本荟萃分析支持的区域值得在未来的研究中密切关注。
A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (PSR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for ‘aggregate’ genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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影响因子：
9.8
作者：
Gurling, HMD;Kalsi, G;Curtis, D
通讯作者：
Curtis, D
影响因子：
17.7
作者：
Faraone, Stephen V.;Hwu, Hai-Gwo;Tsuang, Ming T.
通讯作者：
Tsuang, Ming T.
影响因子：
4.5
作者：
Garver, DL;Holcomb, J;Barnes, B
通讯作者：
Barnes, B
DOI：
10.1073/pnas.1432927100
发表时间：
2003-07-22
影响因子：
11.1
作者：
Gerber, DJ;Hall, D;Tonegawa, S
通讯作者：
Tonegawa, S
DOI：
10.1002/ajmg.10538
发表时间：
2002-07-08
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
DeLisi, LE;Mesen, A;Sherrington, R
通讯作者：
Sherrington, R