Polygenic Analysis of Late-Onset Alzheimer's Disease from Mainland China.
Polygenic Analysis of Late-Onset Alzheimer's Disease from Mainland China.
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中国大陆迟发性阿尔茨海默病的多基因分析
DOI：
10.1371/journal.pone.0144898
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Shen L
中科院分区：
文献类型：
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作者：
Jiao B;Liu X;Zhou L;Wang MH;Zhou Y;Xiao T;Zhang W;Sun R;Waye MM;Tang B;Shen L
最近，通过全基因组关联研究数据，许多单核苷酸多态性（SNP）与晚期发作的阿尔茨海默氏病（负载）有关。 SNP-SNP相互作用的识别在更好地理解负载的遗传基础方面起着重要作用。在这项研究中，在中国大陆的229例负载病例和318个对照组中筛选了58个SNP，并通过一系列分析方法评估它们的相互作用。确定七个风险SNP和六个保护性SNP与负载相关。风险SNP包括RS9331888（CLU），RS6691117（CR1），RS4938933（MS4A），RS9349407（CD2AP），RS1160985（TOMM40），RS4945261（GAB2）（GAB2）和RS598888888894（tomm40）;保护性SNP由RS744373（BIN1），RS1562990（MS4A），RS597668（EXOC3L2），RS9271192（HLA-DRB5/DRB1），RS157581和RS115556505（Tomm40）组成。在上面介绍的正SNP中，我们发现MS4A中的RS4938933（风险）和1562990卢比（保护性）之间的相互作用削弱了其对负载的效果。对于Tomm40中的三个有效的SNP，它们的累积相互作用诱导了两种保护性SNP效应损失，并使载荷的风险SNP效应加剧了。 Finally, we found rs6656401-rs3865444 (CR1-CD33) pairs were significantly associated with decreasing LOAD risk, while rs28834970-rs6656401 (PTK2B-CR1), and rs28834970-rs6656401 (PTK2B-CD33) were associated with increasing LOAD risk.在一个词中，我们的研究表明SNP-SNP相互作用存在于同一基因或跨不同基因中，这可能会削弱或加剧其最初的单一效应以实现负载。
Recently, a number of single nucleotide polymorphisms (SNPs) were identified to be associated with late-onset Alzheimer disease (LOAD) through genome-wide association study data. Identification of SNP-SNP interaction played an important role in better understanding genetic basis of LOAD. In this study, fifty-eight SNPs were screened in a cohort of 229 LOAD cases and 318 controls from mainland China, and their interaction was evaluated by a series of analysis methods. Seven risk SNPs and six protective SNPs were identified to be associated with LOAD. Risk SNPs included rs9331888 (CLU), rs6691117 (CR1), rs4938933 (MS4A), rs9349407 (CD2AP), rs1160985 (TOMM40), rs4945261 (GAB2) and rs5984894 (PCDH11X); Protective SNPs consisted of rs744373 (BIN1), rs1562990 (MS4A), rs597668 (EXOC3L2), rs9271192 (HLA-DRB5/DRB1), rs157581 and rs11556505 (TOMM40). Among positive SNPs presented above, we found the interaction between rs4938933 (risk) and rs1562990 (protective) in MS4A weakened their each effect for LOAD; for three significant SNPs in TOMM40, their cumulative interaction induced the two protective SNPs effects lost and made the risk SNP effect aggravate for LOAD. Finally, we found rs6656401-rs3865444 (CR1-CD33) pairs were significantly associated with decreasing LOAD risk, while rs28834970-rs6656401 (PTK2B-CR1), and rs28834970-rs6656401 (PTK2B-CD33) were associated with increasing LOAD risk. In a word, our study indicates that SNP-SNP interaction existed in the same gene or cross different genes, which could weaken or aggravate their initial single effects for LOAD.