Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Master of Public Health Degree Program, College of Public Health, National Taiwan University, Taipei, Taiwan.
Hum Mol Genet. 2022 Jun 4;31(11):1860-1870. doi: 10.1093/hmg/ddab369.
To highlight the genetic architecture for epigenetic aging, McCartney et al. recently identified 137 significant single-nucleotide polymorphisms based on genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and two epigenetic surrogate markers. However, none Asian ancestry studies have been included in this or previous meta-analyses. I performed a GWAS on blood DNA methylation (DNAm) levels of 2309 Taiwan Biobank (TWB) participants. Owing to the fact that the sample size of an individual GWAS of DNAm data is still not large, I adopted the 'prioritized subset analysis' (PSA) method to boost the power of a GWAS. The four epigenetic clocks and the two epigenetic surrogate markers were investigated, respectively. I replicated 21 out of the 137 aging-associated genetic loci by applying the PSA method to the TWB DNAm data. Moreover, I identified five novel loci, including rs117530284 that was associated with the 'epigenetic age acceleration' (EAA) according to Lu et al.'s GrimAge (called 'GrimEAA'). Considering 16 covariates (sex, BMI, smoking status, drinking status, regular exercise, educational attainment and the first 10 ancestry principal components), each 'A' allele of rs117530284 in the IBA57 gene was found to be associated with a 1.5943-year GrimEAA (95% confidence interval = [1.0748, 2.1138]). IBA57 is a protein coding gene and is associated with multiple mitochondrial dysfunctions syndromes. A decline in mitochondrial activity and quality is associated with aging and many age-related diseases. This is one of the first DNAm GWAS for individuals of Asian ancestry.
为了突出表观遗传衰老的遗传结构，McCartney 等人最近根据四个表观遗传时钟和两个表观遗传替代标志物的全基因组关联研究（GWAS）荟萃分析，确定了 137 个显著的单核苷酸多态性。然而，在这或之前的荟萃分析中，均未包含亚洲血统的研究。我对 2309 名台湾生物银行（TWB）参与者的血液 DNA 甲基化（DNAm）水平进行了 GWAS。由于个体 DNAm 数据的 GWAS 样本量仍然不大，我采用了“优先子集分析”（PSA）方法来提高 GWAS 的功效。分别研究了四个表观遗传时钟和两个表观遗传替代标志物。通过 PSA 方法应用于 TWB DNAm 数据，我复制了 137 个与衰老相关的遗传位点中的 21 个。此外，我鉴定了五个新的位点，包括 rs117530284，该位点与 Lu 等人的 GrimAge（称为“GrimEAA”）相关联。考虑到 16 个协变量（性别、BMI、吸烟状态、饮酒状态、规律运动、教育程度和前 10 个祖先主成分），IBA57 基因中 rs117530284 的每个“A”等位基因与 1.5943 岁的 GrimEAA 相关（95%置信区间[1.0748, 2.1138]）。IBA57 是一个蛋白编码基因，与多种线粒体功能障碍综合征相关。线粒体活性和质量的下降与衰老和许多与年龄相关的疾病有关。这是亚洲血统个体的第一个 DNAm GWAS 之一。
