Sex-specific association of the Reelin gene with bipolar disorder.
Sex-specific association of the Reelin gene with bipolar disorder.
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DOI：
10.1002/ajmg.b.31018
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发表时间：
2010-03-05
影响因子：
2.8
通讯作者：
Potash, J. B.
中科院分区：
文献类型：
--
作者：
Goes, F. S.;Willour, V. L.;Zandi, P. P.;Belmonte, P. L.;MacKinnon, D. F.;Mondimore, F. M.;Schweizer, B.;DePaulo, J. R., Jr.;Gershon, E. S.;McMahon, F. J.;Potash, J. B.
Reelin基因（Reelin gene，CRN）编码一种对大脑发育和突触可塑性至关重要的分泌性糖蛋白。尸检研究表明，与对照组相比，精神分裂症和双相情感障碍（BP）患者大脑中的Reelin蛋白水平较低。在最近的一项精神分裂症全基因组关联研究中，最强的关联被发现在一个标志物中，尽管这种关联只在女性中发现。在这项研究中，我们调查了在一个大的家庭样本中，是否遗传变异在BPN与BP。我们对来自318个核心家庭的1，188个个体（包括554个受影响的后代）进行了75个tagSNPs和6个编码SNPs的基因分型。质量控制措施，传输不平衡测试（TDTs），并在PLINK进行实证模拟。我们发现rs362719的C等位基因向BP后代的显著过度传递（OR = 1.47，P = 5.9 × 10-4）;这经受住了多标记物检验的经验校正（经验P = 0.048）。在一项假设驱动的二次分析中，我们发现与rs362719的关联几乎完全是由假定的风险等位基因向受影响女性的过度传播所解释的（OR女性= 1.79，P = 8.9 × 10-5 vs. OR男性= 1.12，P = 0.63）。这些结果提供了初步的证据表明，遗传变异在BPN与BP的易感性，特别是对BP的女性。然而，我们的研究结果应谨慎解释，直到进一步的复制和功能检测提供趋同的支持。
The Reelin gene (RELN) encodes a secretory glycoprotein critical for brain development and synaptic plasticity. Post-mortem studies have shown lower Reelin protein levels in the brains of patients with schizophrenia and bipolar disorder (BP) compared with controls. In a recent genome-wide association study of schizophrenia, the strongest association was found in a marker within RELN, although this association was seen only in women. In this study, we investigated whether genetic variation in RELN is associated with BP in a large family sample. We genotyped 75 tagSNPs and 6 coding SNPs in 1,188 individuals from 318 nuclear families, including 554 affected offspring. Quality control measures, transmission-disequilibrium tests (TDTs), and empirical simulations were performed in PLINK. We found a significant overtransmission of the C allele of rs362719 to BP offspring (OR = 1.47, P = 5.9 × 10–4); this withstood empirical correction for testing of multiple markers (empirical P = 0.048). In a hypothesis-driven secondary analysis, we found that the association with rs362719 was almost entirely accounted for by overtransmission of the putative risk allele to affected females (ORFemale = 1.79, P = 8.9 × 10–5 vs. ORMale = 1.12, P = 0.63). These results provide preliminary evidence that genetic variation in RELN is associated with susceptibility to BP and, in particular, to BP in females. However, our findings should be interpreted with caution until further replication and functional assays provide convergent support.
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影响因子：
4.4
作者：
Royaux, I;deRouvroit, CL;Goffinet, AM
通讯作者：
Goffinet, AM
影响因子：
5.3
作者：
Chen, Y;Beffert, U;Herz, J
通讯作者：
Herz, J
影响因子：
11
作者：
Badner, JA;Gershon, ES
通讯作者：
Gershon, ES
影响因子：
3.4
作者：
Barr, Alasdair M.;Fish, Kenneth N.;Honer, William G.
通讯作者：
Honer, William G.
DOI：
10.1002/ajmg.b.30726
发表时间：
2008-10-05
影响因子：
2.8
作者：
Kahler, Anna K.;Djurovic, Srdjan;Andreassen, Ole A.
通讯作者：
Andreassen, Ole A.