Nazarian Alireza, Cook Brandon, Morado Marissa, Kulminski Alexander M
Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27705, USA.
Genes (Basel). 2023 Aug 23;14(9):1666. doi: 10.3390/genes14091666.
Sporadic Alzheimer's disease (AD) is a polygenic neurodegenerative disorder. Single-nucleotide polymorphisms (SNPs) in multiple genes (e.g., and ) have been associated with AD. However, none of them were characterized as causal variants that indicate the complex genetic architecture of AD, which is likely affected by individual variants and their interactions. We performed a meta-analysis of four independent cohorts to examine associations of 32 and 50 polymorphisms as well as their 496 and 1225 pair-wise interactions with AD. The single SNP analyses revealed that six and five SNPs were associated with AD. Ten of them were previously not reported. The interaction analyses identified AD-associated compound genotypes for 25 and 24 SNP pairs, whose comprising SNPs were not associated with AD individually. Three and one additional and pairs composed of the AD-associated SNPs showed partial interactions as the minor allele effect of one SNP in each pair was intensified in the absence of the minor allele of the other SNP. The interactions identified here may modulate associations of the and variants with AD. Our analyses highlight the importance of the roles of combinations of genetic variants in AD risk assessment.
散发性阿尔茨海默病（AD）是一种多基因神经退行性疾病。多个基因（如……和……）中的单核苷酸多态性（SNP）与AD相关。然而，它们中没有一个被确定为因果变异，这表明AD的复杂遗传结构可能受到个体变异及其相互作用的影响。我们对四个独立队列进行了荟萃分析，以研究32个……和50个……多态性及其496对和1225对两两相互作用与AD的关联。单SNP分析显示，六个……和五个……SNP与AD相关。其中十个以前未被报道。相互作用分析确定了25对……和24对……SNP对的AD相关复合基因型，其组成SNP单独与AD不相关。由AD相关SNP组成的另外三对……和一对……显示出部分相互作用，因为每对中一个SNP的次要等位基因效应在另一个SNP的次要等位基因不存在时增强。这里确定的相互作用可能调节……和……变异与AD的关联。我们的分析强调了基因变异组合在AD风险评估中的作用的重要性。
