Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14
Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14
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DOI：
10.1038/sj.mp.4001815
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发表时间：
2006-07-01
影响因子：
11
通讯作者：
Leboyer, M.
中科院分区：
文献类型：
--
作者：
Etain, B.;Mathieu, F.;Leboyer, M.
初步研究表明，发病年龄（AAO）可能有助于确定同质双相情感障碍（BPAD）亚型。这种候选症状的方法可能是有用的，以确定脆弱性基因。因此，通过关注早发性BPAD I型先证者的家族，可能会增加检测主要致病基因的概率。本研究作为早发性BPAD欧洲合作研究（法国、德国、爱尔兰、苏格兰、瑞士、英格兰、斯洛文尼亚）的一部分进行。我们进行了全基因组搜索384个微卫星标记使用非参数连锁分析，在87同胞对确定通过早发性BPAD I型先证者（AAO的21岁或以下）。非参数多点分析显示8个连锁区域P值< 0.01（2 p21，2q14.3，3 p14，5 q33，7 q36，10 q23，16 q23和20 p12）。3 p14区域显示出最显著的连锁（全基因组P值估计超过0.015 [ 0.01 - 0.02]的10000次模拟重复）。全基因组搜索分析后，我们进行了额外的连锁分析，增加标记密度使用标记在四个区域暗示连锁和具有低于75%的信息含量（3 p14，10 q23，16 q23和20 p12）。这些区域的信息含量提高了约10%。在3号染色体中，非参数连锁评分从3.51增加到3.83。这项研究是第一次使用早发双相I型先证者，试图增加样本的均匀性。这些初步调查结果需要在独立的家庭小组中确认。
Preliminary studies suggested that age at onset ( AAO) may help to define homogeneous bipolar affective disorder ( BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD ( France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non-parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband ( AAO of 21 years or below). Nonparametric multipoint analysis suggested eight regions of linkage with P-values < 0.01 ( 2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage ( genome-wide P- value estimated over 10 000 simulated replicates of 0.015 [ 0.01 - 0.02]). After genome-wide search analysis, we performed additional linkage analyses with increased marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% ( 3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non-parametric linkage score increased from 3.51 to 3.83. This study is the first to use early-onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families.