Genomewide linkage analyses of bipolar disorder: A new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative
Genomewide linkage analyses of bipolar disorder: A new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative
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DOI：
10.1086/376562
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发表时间：
2003-07-01
影响因子：
9.8
通讯作者：
Nurnberger, JI
中科院分区：
文献类型：
--
作者：
Dick, DM;Foroud, T;Nurnberger, JI
我们对来自250个双相情感障碍及相关情感疾病家系的1152名个体进行了全基因组连锁分析。这些家系是在美国的10个地点确定的，通过一名患有双相I型情感障碍的先证者以及一名患有双相I型或分裂情感性障碍（双相型）的兄弟姐妹来确定。所有地点都使用了统一的确定和评估方法。使用391个标记进行了9 - cM的筛查，平均杂合度为0.76。在患病亲属对中进行了多点、非参数连锁分析。此外，还进行了模拟分析以确定本研究的全基因组显著性水平。分析了三种情感的分层模型。在17号染色体长臂（17q）上发现了显著的连锁证据（全基因组P <.10），在标记D17S928处最大LOD值为3.63，在6号染色体长臂（6q）上，在标记D6S1021附近最大LOD值为3.61。这些基因座符合全基因组显著性的标准和基于模拟的标准。在其他三个区域观察到了连锁的提示性证据（全基因组P
We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P < .10) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P