Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women.
Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women.
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DOI：
10.1371/journal.pgen.0040028
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发表时间：
2008-02
期刊：
影响因子：
4.5
通讯作者：
Darvasi A
中科院分区：
文献类型：
--
作者：
Shifman S;Johannesson M;Bronstein M;Chen SX;Collier DA;Craddock NJ;Kendler KS;Li T;O'Donovan M;O'Neill FA;Owen MJ;Walsh D;Weinberger DR;Sun C;Flint J;Darvasi A
精神分裂症的性别差异是众所周知的，但其遗传基础尚未确定。我们使用DNA池对德系犹太人群体中的精神分裂症进行了全基因组关联扫描。我们发现与rs7341475（reelin（RELN）基因第四内含子中的SNP）存在女性特异性关联（女性p = 2.9 × 10 - 5），具有显着的基因性别效应（p = 1.8 × 10 - 4）。我们在另外四个人群中研究了rs7341475，共计2，274例病例和4，401例对照。仅在女性中观察到显著的影响，复制了最初的结果（女性p = 2.1 × 10−3;基因-性别相互作用p = 4.2 × 10−3）。基于所有人群，携带常见基因型的女性的估计相对风险为1.58（p = 8.8 × 10−7;基因-性别相互作用p = 1.6 × 10−5）。女性特异性的关联性，是在任何疾病中复制的性别特异性遗传关联的少数例子之一。精神分裂症是一种复杂的精神疾病，包括妄想、幻觉、言语混乱、行为异常、缺乏情感表达、动机减弱和社交退缩等症状。精神分裂症的病因尚不清楚，但有大量证据表明遗传学在其病因学中起着重要作用。我们通过分析精神分裂症患者和对照组DNA中分布在整个人类基因组中的大约50万个遗传变异来研究精神分裂症的遗传基础。我们分别分析了男性和女性的DNA，并确定了一种只增加女性患精神分裂症风险的遗传变异。据估计，这种遗传变异会使携带这种风险变异的妇女患精神分裂症的风险增加1.4倍。这种基因变异存在于一种名为reelin的基因中，该基因已知在大脑发育中起作用。然而，目前还不清楚这种遗传变异如何导致精神分裂症，也不清楚为什么它只针对女性。
Sex differences in schizophrenia are well known, but their genetic basis has not been identified. We performed a genome-wide association scan for schizophrenia in an Ashkenazi Jewish population using DNA pooling. We found a female-specific association with rs7341475, a SNP in the fourth intron of the reelin (RELN) gene (p = 2.9 × 10−5 in women), with a significant gene-sex effect (p = 1.8 × 10−4). We studied rs7341475 in four additional populations, totaling 2,274 cases and 4,401 controls. A significant effect was observed only in women, replicating the initial result (p = 2.1 × 10−3 in women; p = 4.2 × 10−3 for gene-sex interaction). Based on all populations the estimated relative risk of women carrying the common genotype is 1.58 (p = 8.8 × 10−7; p = 1.6 × 10−5 for gene-sex interaction). The female-specific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease. Schizophrenia is a complex mental disease, which includes symptoms of delusions, hallucinations, disorganized speech, aberrant behavior, lack of emotional expression, diminished motivation, and social withdrawal. The cause of schizophrenia is unknown, but there is extensive evidence that genetics play a significant role in its aetiology. We studied the genetic basis of schizophrenia by analyzing around 500,000 genetic variants distributed across the whole human genome in DNA from schizophrenic patients and controls. We analyzed separately the DNA from men and women, and identified a genetic variant that increases the risk of developing schizophrenia in women only. The genetic variant is estimated to increase the risk of schizophrenia for women carrying the risk variant by 1.4-fold. The genetic variant is in a gene called reelin, which is known to play a part in brain development. However, it is still unclear how this genetic variant predisposes to schizophrenia nor why it is specific to women only.
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影响因子：
4.4
作者：
Meaburn, E;Butcher, LM;Liu, L;Fernandes, C;Hansen, V;Al-Chalabi, A;Plomin, R;Craig, I;Schalkwyk, LC
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作者：
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DOI：
10.1002/ajmg.b.30191
发表时间：
2005-08-05
影响因子：
2.8
作者：
Goldberger, C;Gourion, D;Krebs, MO
通讯作者：
Krebs, MO