Family-based association of YWHAH in psychotic bipolar disorder.
Family-based association of YWHAH in psychotic bipolar disorder.
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DOI：
10.1002/ajmg.b.30927
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发表时间：
2009-10-05
影响因子：
2.8
通讯作者：
Potash, James B.
中科院分区：
文献类型：
--
作者：
Grover, Deepak;Verma, Ranjana;Goes, Fernando S.;Mahon, Pamela L. Belmonte;Gershon, Elliot S.;McMahon, Francis J.;Potash, James B.
YWHAH是精神分裂症和双相情感障碍(BP)的位置和功能候选基因。该基因此前已被证明与这两种疾病相关，染色体位置(22q12.3)已多次被认为与这些疾病的连锁研究有关。它编码14-3-3蛋白家族的η亚型，主要在脑内表达，并参与HPA轴的调节。我们在大样本中调查了YWHAH与BP的关系，样本包括来自318个核心家庭的1211名受试者，其中包括554名患病的后代。我们测试了与标准BP表型以及由精神病和情绪不一致特征定义的亚型的相关性。我们对该基因中存在的5个标签SNPs和(GCCTGCA)n多态位进行了基因分型。以家族为基础的关联检验发现，rs2246704与BP(OR1.31，P=0.03)和精神病性BP(OR=1.66，P=0.002)相关。多态重复序列和另外两个SNPs也与精神病性BP有一定的关联。我们已经提供了更多的证据，证明YWHAH的变异与严重的精神疾病有关。还需要对更大的样本集进行额外的关联分析，以澄清YWHAH在精神分裂症和BP中的作用。使用临床亚型，如精神病特征或其他潜在的精神分裂症/血压重叠变量，包括认知异常和功能低下，可能会进一步揭示与YWHAH基因变异最密切相关的潜在疾病亚型。
YWHAH is a positional and functional candidate gene for both schizophrenia and bipolar disorder (BP). This gene has been previously shown to be associated with both disorders, and the chromosome location (22q12.3) has been repeatedly implicated in linkage studies for these disorders. It codes for the η subtype of the 14-3-3 protein family, is expressed mainly in brain, and is involved in HPA axis regulation. We investigated the association of YWHAH with BP in a large sample, consisting of 1211 subjects from 318 nuclear families including 554 affected offspring. We tested for association with the standard BP phenotype as well as subtypes defined by psychotic and mood-incongruent features. We genotyped five tag SNPs and the (GCCTGCA)n polymorphic locus present in this gene. Using a family-based association test, we found that rs2246704 was associated with BP (OR 1.31, P = 0.03) and psychotic BP (OR = 1.66, P = 0.002). The polymorphic repeat and two other SNPs were also modestly associated with psychotic BP. We have provided additional evidence for association of variants in YWHAH with major mental illness. Additional association analyses of larger sample sets will be required to clarify the role of YWHAH in schizophrenia and BP. The use of clinical sub-phenotypes such as psychotic features or other potential schizophrenia/BP overlap variables including cognitive abnormalities and poor functioning might shed further light on the potential subtypes of illness most closely associated with genetic variation in YWHAH.
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影响因子：
5.2
作者：
Horvath, S;Xu, X;Laird, NM
通讯作者：
Laird, NM
DOI：
10.1073/pnas.96.10.5604
发表时间：
1999-05-11
影响因子：
11.1
作者：
Detera-Wadleigh, SD;Badner, JA;Gershon, ES
通讯作者：
Gershon, ES
影响因子：
14.9
作者：
Grover, Deepak;Woodfield, Alonzo S.;Potash, James B.
通讯作者：
Potash, James B.
影响因子：
17.7
作者：
Potash, James B.;Toolan, Jennifer;McMahon, Francis J.
通讯作者：
McMahon, Francis J.
影响因子：
11
作者：
Baum, A. E.;Akula, N.;McMahon, F. J.
通讯作者：
McMahon, F. J.