Early onset bipolar disorder: possible linkage to chromosome 9q34
Early onset bipolar disorder: possible linkage to chromosome 9q34
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DOI：
10.1111/j.1399-5618.2006.00289.x
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发表时间：
2006-04-01
影响因子：
5.4
通讯作者：
Tsuang, MT
中科院分区：
文献类型：
--
作者：
Faraone, SV;Lasky-Su, J;Tsuang, MT
目的：双相情感障碍（BD）以躁狂和抑郁状态为特征，在生命的不同时期发作。研究表明，早发型双相障碍与更强的疾病遗传负荷有关。我们假设，在遗传连锁分析中使用发病年龄来观察双相障碍家族亚群，将证明有助于分离病因同质的双相障碍亚群，并随后确定遗传易感区域。方法：我们使用wave-I国家精神卫生研究所（NIMH）遗传学倡议双相障碍样本，其中包括来自97个双相障碍家庭的540名个体，在以躁狂发病年龄作为子集识别协变量的有序亚群连锁分析中。使用genehunt - plus进行分析，然后使用有序子集分析程序。该程序生成具有最大LOD分数的子集的经验p值，以确定该值是否显著高于使用所有家庭的基线LOD分数。结果：LOD评分高于2.0的染色体区域分别为2.21 （6q25）、3.21 （9q34）和2.16 （20q11）。在58个20岁以前有躁狂发作的家庭中，9q34染色体标记D9S290和D9S915之间的LOD评分增加最大。最小躁狂发作少于20年的家庭有更多的精神合并症（p = 0.02）和抑郁症状的轻微增加（p = 0.10）。结论：有必要对染色体9q34区域进行进一步研究，以确定该区域是否含有最低发病年龄小于20岁的家族特有的基因。
Objectives: Bipolar disorder (BD) is characterized by manic and depressive states that onset at various times in life. Research shows that early onset forms of BD are associated with a stronger genetic loading for the illness. We hypothesized that using age at onset to look at subsets of BD families in a genetic linkage analysis would prove useful in separating etiologically homogeneous BD sub-groups and subsequently identifying genetic susceptibility regions.Methods: We used the wave-I National Institute of Mental Health (NIMH) Genetics Initiative BD sample, which includes 540 individuals from 97 families with BD, in an ordered-subsets linkage analysis with age at onset of mania as the subset-identifying covariate. This analysis was performed using GENEHUNTER-PLUS followed by the ordered-subsets analysis program. This program generates empirical p-values for the subset with the largest LOD score to determine whether this value was significantly higher than the baseline LOD score using all families.Results: Three chromosomal regions resulted in LOD scores above 2.0: 2.21 (6q25), 3.21 (9q34), and 2.16 (20q11). The largest increase in LOD score was observed on chromosome 9q34 between markers D9S290 and D9S915 in the subset of 58 families that had mania onset before age 20. Families with a minimal mania onset less than 20 years had a significantly greater number of psychiatric comorbidities (p = 0.02) and a marginal increase in depressive symptoms (p = 0.10).Conclusions: Further investigation into chromosomal region 9q34 is necessary to determine whether this region may harbor a gene specific to families with a minimal age at onset of less than 20.