Are Alzheimer's and coronary artery diseases genetically related to longevity?

Are Alzheimer's and coronary artery diseases genetically related to longevity?
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DOI:
10.3389/fpsyt.2022.1102347
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发表时间:
2022
影响因子:
4.7
通讯作者:
Escott-Price, Valentina
Escott-Price, Valentina
中科院分区:
医学3区
文献类型:
--
作者:
Bellou, Eftychia;Escott-Price, Valentina

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在过去的十年中,研究人员试图调查长寿和年龄相关疾病的共同遗传结构,并评估某些人的长寿是否是由于特定条件的风险基因中的保护等位基因,或者是否有特定的“长寿”基因独立于年龄相关疾病的风险基因而增加寿命。这项研究的目的是调查长寿和两种年龄相关疾病之间的共同遗传成分。我们使用R软件包ASSET提供的基于子集的方法,对阿尔茨海默病、冠状动脉疾病和寿命的公开全基因组数据进行了跨特质荟萃分析。尽管长寿和这两种疾病之间缺乏强的遗传相关性,但我们在22个独立的基因组基因座中确定了38个全基因组显著的前导SNP。其中6个性状在定位到基因DAB2IP、DNM2、FCHO1、CLPTM1和SNRPD2的3个性状之间存在潜在共享。在这项研究中,我们还确定了19个新的基因组范围内的个体特征关联。功能注释和生物学途径富集分析表明,多效性变体参与网格蛋白介导的内吞作用和血浆脂蛋白和神经递质清除过程。总之,我们已经能够推进在长寿和两个最常见的年龄相关疾病之间存在的遗传重叠的知识。
In the last decade researchers have attempted to investigate the shared genetic architecture of longevity and age-related diseases and assess whether the increased longevity in certain people is due to protective alleles in the risk genes for a particular condition or whether there are specific “longevity” genes increasing the lifespan independently of age-related conditions' risk genes. The aim of this study was to investigate the shared genetic component between longevity and two age-related conditions. We performed a cross-trait meta-analysis of publicly available genome-wide data for Alzheimer's disease, coronary artery disease and longevity using a subset-based approach provided by the R package ASSET. Despite the lack of strong genetic correlation between longevity and the two diseases, we identified 38 genome-wide significant lead SNPs across 22 independent genomic loci. Of them 6 were found to be potentially shared among the three traits mapping to genes including DAB2IP, DNM2, FCHO1, CLPTM1, and SNRPD2. We also identified 19 novel genome-wide associations for the individual traits in this study. Functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants are involved in clathrin-mediated endocytosis and plasma lipoprotein and neurotransmitter clearance processes. In summary, we have been able to advance in the knowledge of the genetic overlap existing among longevity and the two most common age-related disorders.
DOI: 10.1038/s41588-022-01024-z
发表时间: 2022-04
期刊: NATURE GENETICS
影响因子: 30.8
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影响因子: 9.8
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