A pilot genome wide association and gene expression array study of suicide with and without major depression.
A pilot genome wide association and gene expression array study of suicide with and without major depression.
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DOI：
10.3109/15622975.2011.597875
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Mann JJ
中科院分区：
文献类型：
--
作者：
Galfalvy H;Zalsman G;Huang YY;Murphy L;Rosoklija G;Dwork AJ;Haghighi F;Arango V;Mann JJ
自杀在一定程度上是可遗传的，但负责任的基因尚未被确定。我们进行了一项以基因为中心、低覆盖单核苷酸多态性（SNP）的先导全基因组关联研究（GWAS），结合脑组织基因表达分析，寻找伴有和不伴有抑郁症的自杀的新候选区域。99名高加索受试者，包括68名自杀者和31名因其他原因突然死亡的人，在死后使用GeneChip®Mapping 50K Xba进行基因分型。临床资料来自亲属。Hardy - Weinberg平衡P值低于0.001的snp被排除在分析之外。Illumina芯片表达阵列检测了无药物亚组前额叶皮层的转录组。GWAS分析（截止P < 0.001）得到58个snp，其中22个位于或接近19个已知基因，风险等位基因相关比值比在2.7至6.9之间。对情绪障碍的诊断并不能解释这种关联。部分snp与基因本体的四个功能群相匹配。这19个基因在前额叶和前扣带皮层的基因表达是在一个单独的自杀样本上测量的，尽管有重叠，与对照组相比，19个基因中有7个基因的表达发生了改变，尤其是在免疫系统相关的基因中。将GWAS研究结果与表达数据相匹配，评估了新的候选基因在自杀中的功能影响，是确认或复制研究的另一种形式。结果强调了神经免疫效应在自杀行为中的作用。
Suicide is partly heritable but the responsible genes have not been identified. We conducted a gene-centric, low coverage single nucleotide polymorphism (SNP) pilot genome-wide association study (GWAS) seeking new candidate regions in suicides with and without depression, combined with gene expression assay of brain tissue. Ninety-nine Caucasian subjects, including 68 who completed suicide and 31 who died suddenly from other causes, were genotyped postmortem using GeneChip® Mapping 50K Xba. Clinical data were obtained from relatives. SNPs with Hardy – Weinberg equilibrium P values below 0.001 were excluded from analysis. Illumina chip expression arrays assayed the transcriptome in prefrontal cortex in a drug-free subgroup. GWAS analysis (cutoff P < 0.001) yielded 58 SNPs, 22 of them in or near 19 known genes, with risk allele-associated odds ratios between 2.7 and 6.9. Diagnosis of mood disorder did not explain the associations. Some of the SNPs matched into four functional groups in gene ontology. Gene expression in the prefrontal and the anterior cingulate cortex for these 19 genes was measured on a separate, though overlapping, sample of suicides and seven of 19 genes showed altered expression in suicides as compared with controls, especially in immune system related genes. Matching GWAS findings with expression data assesses functional effect of new candidate genes in suicide, and is an alternative form of confirmation or replication study. Results highlight a role for neuroimmunological effects in suicidal behaviour.
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影响因子：
2.6
作者：
Laje G;Allen AS;Akula N;Manji H;John Rush A;McMahon FJ
通讯作者：
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影响因子：
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作者：
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影响因子：
2.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
TRASKMANBENDZ, L