Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population.
Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population.
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DOI：
10.1016/j.schres.2011.06.024
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发表时间：
2011-09
影响因子：
4.5
通讯作者：
Vawter, Marquis P.
中科院分区：
文献类型：
--
作者：
Moon, Emily;Rollins, Brandi;Mesen, Andrea;Sequeira, Adolfo;Myers, Richard M.;Akil, Huda;Watson, Stanley J.;Barchas, Jack;Jones, Edward G.;Schatzberg, Alan;Bunney, William E.;DeLisi, Lynn E.;Byerley, William;Vawter, Marquis P.
关键词：
据报道，NRG 1基因第11外显子的错义多态性瓦尔> Leu可增加来自哥斯达黎加中央谷地区（CVCR）的选定家族患精神分裂症的风险。本研究调查了3个NRG 1基因变异体rs6994992、rs3924999和外显子11中瓦尔> Leu错义多态性之间的关系。孤立的群体可以具有较小的遗传异质性，并增加检测候选基因中风险变异的能力。受试者与双相情感障碍（BD，n = 358），精神分裂症（SZ，n = 273），或无关的对照组（CO，n = 479）进行基因分型的三个NRG 1变异。在其他研究中，NRG 1启动子多态性（rs6994992）与NRG 1 IV型表达改变相关。在BD、SZ、重度抑郁症（MDD）病例和对照组的死后队列中，探讨了NRG 1 IV型在背外侧前额叶皮层（DLPFC）的表达以及rs6994992基因型对表达的影响。外显子11的错义多态性瓦尔> Leu与精神分裂症无显著相关性，次要等位基因频率为4%，因此我们的样本量不足以检测相关性。然而，我们观察到与对照组相比，rs6994992与DLPFC中NRG 1 IV型表达相关，并且MDD中的表达显著降低。目前的结果虽然是阴性的，但并不排除这些SNP与CVCR中BD和SZ的遗传关联，这可能是由于我们无法检测到的小风险效应和潜在的基因间上位性。在我们的初步研究中，在死后样本中复制了先前的NRG 1 IV型和SNP变异的推定脑特异性亚型表达之间的遗传关系。
A missense polymorphism in the NRG1 gene, Val > Leu in exon 11, was reported to increase the risk of schizophrenia in selected families from the Central Valley region of Costa Rica (CVCR). The present study investigated the relationship between three NRG1 genetic variants, rs6994992, rs3924999, and Val > Leu missense polymorphism in exon 11, in cases and selected controls from an isolated population from the CVCR. Isolated populations can have less genetic heterogeneity and increase power to detect risk variants in candidate genes. Subjects with bipolar disorder (BD, n = 358), schizophrenia (SZ, n = 273), or unrelated controls (CO, n = 479) were genotyped for three NRG1 variants. The NRG1 promoter polymorphism (rs6994992) was related to altered expression of NRG1 Type IV in other studies. The expression of NRG1 type IV in the dorsolateral prefrontal cortex (DLPFC) and the effect of the rs6994992 genotype on expression were explored in a postmortem cohort of BD, SZ, major depressive disorder (MDD) cases, and controls. The missense polymorphism Val > Leu in exon 11 was not significantly associated with schizophrenia as previously reported in a family sample from this population, the minor allele frequency is 4%, thus our sample size is not large enough to detect an association. We observed however an association of rs6994992 with NRG1 type IV expression in DLPFC and a significantly decreased expression in MDD compared to controls. The present results while negative do not rule out a genetic association of these SNPs with BD and SZ in CVCR, perhaps due to small risk effects that we were unable to detect and potential intergenic epistasis. The previous genetic relationship between expression of a putative brain specific isoform of NRG1 type IV and SNP variation was replicated in postmortem samples in our preliminary study.
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影响因子：
17.7
作者：
Kieseppä, T;Partonen, T;Lönnqvist, J
通讯作者：
Lönnqvist, J
影响因子：
--
作者：
Alaerts, Maaike;Ceulemans, Shana;Del-Favero, Jurgen
通讯作者：
Del-Favero, Jurgen
DOI：
10.1073/pnas.0406788101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Evans, SJ;Choudary, PV;Akil, H
通讯作者：
Akil, H
影响因子：
0.9
作者：
Bertisch H;Mesen-Fainardi A;Martin MV;Pérez-Vargas V;Vargas-Rodríguez T;Delgado G;Delgado C;Llach M;LaPrade B;Byerley W;Bunney WE;Vawter MP;DeLisi LE;Pritzker Neuropsychiatric Research Consortium
通讯作者：
Pritzker Neuropsychiatric Research Consortium
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