Beyond Parkinson disease: amyotrophic lateral sclerosis and the axon guidance pathway.
Beyond Parkinson disease: amyotrophic lateral sclerosis and the axon guidance pathway.
复制标题
帕金森氏病超越：肌萎缩性侧索硬化和轴突指导途径。
DOI：
10.1371/journal.pone.0001449
复制
发表时间：
2008-01-16
期刊：
影响因子：
3.7
通讯作者：
Maraganore DM
中科院分区：
文献类型：
--
作者：
Lesnick TG;Sorenson EJ;Ahlskog JE;Henley JR;Shehadeh L;Papapetropoulos S;Maraganore DM
我们最近描述了一种研究复杂疾病的基因组途径方法。我们证明，使用轴突导向通路基因内的单核苷酸多态性（SNP）构建的模型在两个独立的全基因组关联数据集内高度预测帕金森病（PD）的易感性、无PD生存率和PD发病年龄。我们还证明，在我们的最终模型中，以SNP为代表的几个轴突导向通路基因在PD中差异表达。在这里，我们采用我们的基因组途径方法分析了肌萎缩侧索硬化症（ALS）全基因组关联数据集的数据;并证明了使用轴突引导途径基因内的SNP构建的模型对ALS易感性（比值比= 1739.73，p = 2.92×10−60），无ALS生存率（风险比= 149.80，p = 1.25×10−74）和ALS发病年龄（R2 = 0.86，p = 5.96×10−66）具有高度预测性。 我们还扩展了对PD全基因组关联数据集的分析，该数据集与ALS全基因组关联数据集共有320，202个基因组SNP。我们比较了ALS和PD的易感性、无病生存率和发病年龄的最终模型中由SNP代表的基因，并注意到分别有52.2%、37.8%和34.9%的基因是共享的。我们对轴突引导通路和ALS的研究结果具有先前的生物相容性，与PD部分重叠，并可能为这些和相关神经退行性疾病的原因提供重要的见解。
We recently described a genomic pathway approach to study complex diseases. We demonstrated that models constructed using single nucleotide polymorphisms (SNPs) within axon guidance pathway genes were highly predictive of Parkinson disease (PD) susceptibility, survival free of PD, and age at onset of PD within two independent whole-genome association datasets. We also demonstrated that several axon guidance pathway genes represented by SNPs within our final models were differentially expressed in PD. Here we employed our genomic pathway approach to analyze data from a whole-genome association dataset of amyotrophic lateral sclerosis (ALS); and demonstrated that models constructed using SNPs within axon guidance pathway genes were highly predictive of ALS susceptibility (odds ratio = 1739.73, p = 2.92×10−60), survival free of ALS (hazards ratio = 149.80, p = 1.25×10−74), and age at onset of ALS (R2 = 0.86, p = 5.96×10−66). We also extended our analyses of a whole-genome association dataset of PD, which shared 320,202 genomic SNPs in common with the whole-genome association dataset of ALS. We compared for ALS and PD the genes represented by SNPs in the final models for susceptibility, survival free of disease, and age at onset of disease and noted that 52.2%, 37.8%, and 34.9% of the genes were shared respectively. Our findings for the axon guidance pathway and ALS have prior biological plausibility, overlap partially with PD, and may provide important insight into the causes of these and related neurodegenerative disorders.
登录
查看更多内容
影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
影响因子：
10.4
作者：
Brown, Rebecca C;Lockwood, Alan H;Sonawane, Babasaheb R
通讯作者：
Sonawane, Babasaheb R
影响因子：
2.7
作者：
Eberhart, J;Swartz, ME;Krull, CD
通讯作者：
Krull, CD
影响因子：
5.3
作者：
Feldner, Julia;Reimer, Michell M.;Becker, Catherina G.
通讯作者：
Becker, Catherina G.
影响因子：
14.5
作者：
Corti, Stefania;Locatelli, Federica;Comi, Giacomo P.
通讯作者：
Comi, Giacomo P.