Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts.
Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts.
复制标题
DOI：
10.1038/s41598-022-07567-9
复制
发表时间：
2022-03-03
影响因子：
4.6
通讯作者：
Seo JH
中科院分区：
文献类型：
--
作者：
Jin H;Yoo HJ;Kim YA;Lee JH;Lee Y;Kwon SH;Seo YJ;Lee SH;Koh JM;Ji Y;Do AR;Won S;Seo JH
肌肉减少症是一种与年龄相关的疾病，其特征是骨骼肌质量进行性减少。由于肌肉减少症的遗传生物标志物尚未得到很好的表征，本研究旨在研究相对老年队列中与肌肉减少症相关的遗传变异，使用全基因组关联研究（GWAS）对6961例受试者的瘦体重（LBM）进行荟萃分析。对两个韩国队列进行了分析，并对非典型骨骼肌质量（ASM）和骨骼肌指数进行了亚组GWAS。显著的单核苷酸多态性（SNPs）对基因表达的影响也进行了研究，使用多表达数量性状位点数据集，差异表达基因分析，和基因本体分析。LBM（rs 1187118; rs3768582）和ASM（rs6772958）的新遗传生物标志物被鉴定出来。它们的相关基因RPS 10、NUDT 3、NCF 2、SMG 7和ARPC 5在骨骼肌组织中的表达存在差异，而GPD 1 L则无差异。此外，“mRNA去稳定化”生物过程对于肌肉减少症是丰富的。我们的研究确定了RPS 10，NUDT 3和GPD 1 L作为肌肉减少症的重要遗传生物标志物。这些基因位点与脂肪和能量代谢有关，提示参与代谢失调的基因可能导致年龄相关性肌肉减少症的发病。
Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. As the genetic biomarkers for sarcopenia are not yet well characterised, this study aimed to investigate the genetic variations related to sarcopenia in a relatively aged cohort, using genome-wide association study (GWAS) meta-analyses of lean body mass (LBM) in 6961 subjects. Two Korean cohorts were analysed, and subgroup GWAS was conducted for appendicular skeletal muscle mass (ASM) and skeletal muscle index. The effects of significant single nucleotide polymorphisms (SNPs) on gene expression were also investigated using multiple expression quantitative trait loci datasets, differentially expressed gene analysis, and gene ontology analyses. Novel genetic biomarkers were identified for LBM (rs1187118; rs3768582) and ASM (rs6772958). Their related genes, including RPS10, NUDT3, NCF2, SMG7, and ARPC5, were differently expressed in skeletal muscle tissue, while GPD1L was not. Furthermore, the ‘mRNA destabilisation’ biological process was enriched for sarcopenia. Our study identified RPS10, NUDT3, and GPD1L as significant genetic biomarkers for sarcopenia. These genetic loci were related to lipid and energy metabolism, suggesting that genes involved in metabolic dysregulation may lead to the pathogenesis of age-related sarcopenia.
登录
查看更多内容
影响因子：
4.4
作者：
Chaves DF;Carvalho PC;Lima DB;Nicastro H;Lorenzeti FM;Siqueira-Filho M;Hirabara SM;Alves PH;Moresco JJ;Yates JR 3rd;Lancha AH Jr
通讯作者：
Lancha AH Jr
影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
4.6
作者：
Arce-Cerezo A;García M;Rodríguez-Nuevo A;Crosa-Bonell M;Enguix N;Peró A;Muñoz S;Roca C;Ramos D;Franckhauser S;Elias I;Ferre T;Pujol A;Ruberte J;Villena JA;Bosch F;Riu E
通讯作者：
Riu E
影响因子：
64.8
作者：
Han, Zhifu;Niu, Tianhui;Chai, Jijie
通讯作者：
Chai, Jijie
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian