Genetic segregation analysis of recurrent, early-onset major depression: Evidence for single major locus transmission
Genetic segregation analysis of recurrent, early-onset major depression: Evidence for single major locus transmission
复制标题
DOI：
10.1002/ajmg.10158
复制
发表时间：
2002-03-08
期刊：
影响因子：
--
通讯作者：
Zubenko, GS
中科院分区：
文献类型：
--
作者：
Maher, BS;Marazita, ML;Zubenko, GS
目前正在进行协调努力，以确定单相严重抑郁障碍(MDD)和相关疾病的易感基因。这些研究的重点是复发性早发性MDD(RE-MDD)，被认为是这种疾病的最常见的家族形式。这项研究的目的是对反复发作的MDD和其他主要的情绪障碍进行复杂的分离分析，这些疾病聚集在患有RE-MDD先证者的家庭中。通过18岁以上的先证者确定了81个家庭，这些家庭符合复发(大于或等于2次发作)、早发(小于或等于25岁)、非精神病、单相MDD(RE-MDD)的标准，包括407名一级亲属和835名扩展亲属。提供血液样本的先证者及其家人的精神诊断是通过结构化的个人访谈、结构化的家族史评估和可用的医疗记录得出的。其余参与的家庭成员和已故的家庭成员通过家族史方法进行评估，并辅以现有的医疗记录。根据既定的诊断标准，在一次协商一致的会议上做出了最佳估计诊断。使用S.A.G.E.版本4.0中的REGD程序进行分离分析。复发MDD的分离分析支持性别无关的孟德尔共显性模型。对主要情绪障碍的分析支持了性别无关的孟德尔主导模型。有趣的是，包括配偶残留相关性在内的研究为复发的MDD提供了更好的拟合模型，但并不是主要情绪障碍的更广泛的表型。与单相MDD不同，在这个家庭样本中，双相I型障碍的终生流行率没有超过报告的人口流行率[Zubenko等人，2001年]。我们的结果表明，一个主要的基因座有助于复发MDD的表达，并可能在RE-MDD先证者发现的其他主要情绪障碍的家庭中发挥作用。由于分离分析模型的局限性，我们的结果不能说明样本中是否有相同的主基因座在家系中分离，或者是否涉及多个主基因座(遗传异质性)。这些家系中没有双相I型障碍的聚集，这强烈地表明，尽管单相和双相障碍的遗传决定因素可能重叠，但它们并不相同。我们的发现表明，在旨在检测单相MDD和相关疾病的易感基因的研究中，雇用患有RE-MDD的先证者确定的家系具有优势。(C)2002年Wiley-Liss，Inc.
Coordinated efforts are now underway to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders. These studies have focused on recurrent, early-onset MDD (RE-MDD), thought to be the most familial form of this disorder. The goal of this study was to conduct a complex segregation analysis of recurrent MDD and other major mood disorders aggregating in families identified by probands with RE-MDD. Eighty-one families were identified through probands over the age of 18 who met criteria for recurrent (greater than or equal to2 episodes), early-onset (less than or equal to25 years), nonpsychotic, unipolar MDD (RE-MDD) and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best-estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Segregation analyses were performed using the REGD routine in S.A.G.E. release 4.0. The segregation analysis of recurrent MDD supported a sex-independent Mendelian codominant model. Analysis of major mood disorders supported a sex-independent Mendelian dominant model. Interestingly, inclusion of spousal residual correlations provided better fitting models for recurrent MDD but not the broader phenotype of major mood disorders. Unlike unipolar MDD, the lifetime prevalence of bipolar I disorder in this sample of families did not exceed the reported population prevalence [Zubenko et al., 2001]. Our results suggest that a major locus contributes to the expression of recurrent MDD and possibly other major mood disorders within families identified by probands with RE-MDD. Due to the limitations of the segregation analysis model, our results cannot address whether the same major locus is segregating across families in our sample or whether multiple major loci are involved (genetic heterogeneity). The absence of aggregation of bipolar I disorder in these families strongly suggests that while the genetic determinants of unipolar and bipolar disorders may overlap, they are not identical. Our findings illustrate the advantage of employing families identified by probands with RE-MDD in studies designed to detect susceptibility loci for unipolar MDD and related disorders. (C) 2002 Wiley-Liss, Inc.