A genomic scan for age at onset of Alzheimer's disease in 437 families from the NIMH Genetic Initiative.
A genomic scan for age at onset of Alzheimer's disease in 437 families from the NIMH Genetic Initiative.
复制标题
DOI：
10.1002/ajmg.b.30689
复制
发表时间：
2008-09-05
影响因子：
2.8
通讯作者：
Go, Rodney C. P.
中科院分区：
文献类型：
--
作者：
Dickson, M. Ryan;Li, Jian;Wiener, Howard W.;Perry, Rodney T.;Blacker, Deborah;Bassett, Susan S.;Go, Rodney C. P.
我们对阿尔茨海默病（AD）NIMH样本（N = 437个家庭）的发病年龄（AAO）进行了连锁分析。其中晚发家系320个，AAO ≥65;早发/混合家系117个，至少有1名成员AAO <65。将AAO作为删失性状，在参数生存模型中得到性别和APOE的调整残差，并将其作为数量性状（QT）进行方差分量连锁分析。为了进行比较，AAO-检查时年龄（AAE）被分析为QT，根据情感状态、性别和APOE进行调整。残留和AAO-AAE结局的遗传率在总样本中分别为66.3%和74.0%，在晚发型样本中分别为56.0%和57.0%，在早期/混合样本中两种模型的遗传率分别为33.0%。残差模型在第1号染色体上产生了最大峰，在全集中190 cM处的LOD = 2.0，在早期/混合子集中3号染色体上116 cM处的LOD = 1.7，在晚发型子集中6号染色体上71和86 cM处的LOD分别为1.4。对于AAO-AAE结果模型，在1号染色体上137 cM（LOD = 2.8）和6号染色体上69 cM（LOD = 2.3）和86 cM（LOD = 2.2）处鉴定出最大峰，均在晚发型亚组中。在总样品和各子集的1、2、3、6、8、9、10和12号染色体上鉴别出LOD ≥1的其他峰。结果重复了以前的研究结果，但确定了额外的提示峰，表明AD中AAO的遗传学是复杂的，许多染色体区域可能含有修饰基因。
We performed linkage analysis for age at onset (AAO) in the total Alzheimer’s disease (AD) NIMH sample (N = 437 families). Families were subset as late-onset (320 families, AAO ≥65) and early/ mixed (117 families, at least 1 member with 50< AAO <65). Treating AAO as a censored trait, we obtained the gender and APOE adjusted residuals in a parametric survival model and analyzed the residuals as the quantitative trait (QT) in variance-component linkage analysis. For comparison, AAO–age at exam (AAE) was analyzed as the QT adjusting for affection status, gender, and APOE. Heritabilities for residual and AAO–AAE outcomes were 66.3% and 74.0%, respectively for the total sample, 56.0% and 57.0% in the late-onset sample, and 33.0% for both models in the early/mixed sample. The residual model yielded the largest peaks onchromosome1 with LOD = 2.0 at 190 cM in the total set, LOD = 1.7 at 116 cM on chromosome 3 in the early/mixed subset, and LOD = 1.4 at 71 and 86 cM, respectively, on chromosome 6 in the late-onset subset. For the AAO–AAE outcome model the largest peaks were identified on chromosome 1 at 137 cM (LOD = 2.8) and chromosome 6 at 69 cM (LOD = 2.3) and 86 cM (LOD = 2.2) all in the late-onset subset. Additional peaks with LOD ≥1 were identified on chromosomes 1, 2, 3, 6, 8, 9, 10, and 12 for the total sample and each subset. Results replicate previous findings, but identify additional suggestive peaks indicating the genetics of AAO in AD is complex with many chromosomal regions potentially containing modifying genes.
登录
查看更多内容
影响因子：
4
作者：
Bertram, Lars;Mullin, Kristina;Tanzi, Rudolph E.
通讯作者：
Tanzi, Rudolph E.
影响因子：
3.5
作者：
Ertekin-Taner, N;Ronald, J;Younkin, S
通讯作者：
Younkin, S
影响因子：
3.5
作者：
Blacker, D;Bertram, L;Tanzi, RE
通讯作者：
Tanzi, RE
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
9.3
作者：
Bertram, L;Tanzi, RE
通讯作者：
Tanzi, RE