背景:由于肌肉质量下降,肌肉减少症常见于老年人。许多研究人员进行了全基因组关联研究(GWAS),以发现肌肉减少症的遗传风险因素。尽管许多研究发现了肌肉减少症相关的单核苷酸多态性(SNPs),大部分是针对白种人的研究.这项研究的目的是使用韩国基因组和流行病学研究(KOGES)的数据根据中年韩国人的肌肉质量评估遗传相关性,一项基于人群的大型基因组队列研究。
方法:基线参与者是10,030名年龄在40至69岁之间的受试者,他们来自京坪岛的Ansan或Anseong,韩国。其中,本研究包括9,351名具有实验室数据的受试者。为了鉴定肌肉减少症相关变异,肌肉质量指数(MMI)前30%和后30%的人进行了比较.共有7,452名MMI为30-70%的人被排除在外。由于缺少数据,共有1,004人被排除在外。最后,选择895人进行这项研究。韩国生物库阵列为该数据集生成了500,568个SNP。
结果:当受试者分为MMI的前30%和后30%时,前30%有169名男性和308名女性,后30%有220名男性和198名女性。在男人中,年龄,体重指数(BMI),前30%和后30%MMI组的腰部和臀部有显著差异(P<0.005).在女性中,年龄,BMI,腰部,臀部,和高血压病史在两个MMI组之间有显著差异.男性有13个显著SNP,女性有14个显著SNP。基于单核苷酸多态性数据库(dbSNP),与男性变异相关的基因是包含rs11679458的LRP1B和包含rs11848300的RGS6。与女性变异相关的基因是Pi4K2A,其中包含rs1189312作为变体。此外,rs11189312与ZFYVE27在骨骼肌中的表达数量性状基因座(eQTL)以及已知与痉挛性截瘫相关的ZFYVE27的其他SNP(rs10882883,rs17108378,rs35077384)相关。eQTL分析揭示rs11189312是与ZFYVE27的SNP相关的变体。
结论:在人口统计学研究中,在BMI中发现了显著的结果,腰部,臀部,高脂血症史,男性群体中久坐不动的生活状态,在BMI中发现了显著的结果,腰部,臀部,女性组高血压病史。发现变体rs11189312是影响骨骼肌中表达的ZFYVE27的新变体,这表明rs11189312可能与肌少症有关,这是本研究的一个新发现。需要进一步研究以确定已知与痉挛性截瘫相关的肌肉减少症和ZFYVE27之间的关联。
BACKGROUND: Sarcopenia is commonly found in the elderly due to a decline in muscle mass. Many researchers have performed genome-wide association studies (GWAS) to find genetic risk factors of sarcopenia. Although many studies have discovered sarcopenia associated single nucleotide polymorphisms (SNPs), most of them are studies targeting Caucasians. The purpose of this study was to evaluate genetic correlation according to muscle mass in middle aged Koreans using data of the Korean Genome and Epidemiology Study (KOGES), a large population-based genomic cohort study.
METHODS: Baseline participants were 10,030 subjects aged 40 to 69 years who were from Ansan or Anseong in Gyeonggi-do, South Korea. Among them, 9,351 subjects with laboratory data available were included in this study. To identify sarcopenia associated variants, those in the top 30% and bottom 30% of muscle mass index (MMI) were compared. A total of 7,452 people with an MMI of 30-70% were excluded. A total of 1,004 people were also excluded due to missing data. Finally, 895 people were selected for this study. The Korea Biobank Array generated 500,568 SNPs for this dataset.
RESULTS: When subjects were divided into top 30% and bottom 30% of MMI, the top 30% had 169 men and 308 women and the bottom 30% had 220 men and 198 women. In men, age, body mass index (BMI), waist and hip were significantly (P < 0.005) different between top 30% and bottom 30% MMI groups. In women, age, BMI, waist, hip, and hypertension history were significantly different between the two MMI groups. There were 13 significant SNPs in men and 14 significant SNPs in women. Genes associated with variants in men based on the single-nucleotide polymorphism database (dbSNP) were LRP1B containing rs11679458 and RGS6 containing rs11848300. A gene associated with variants in women was Pi4K2A, which contained rs1189312 as a variant. In addition, rs11189312 was associated with expression quantitative trait loci (eQTL) of ZFYVE27 in skeletal muscles and other SNPs of ZFYVE27 (rs10882883, rs17108378, rs35077384) known to be associated with spastic paraplegia. The eQTL analysis revealed that rs11189312 was a variant associated with SNPs of ZFYVE27.
CONCLUSIONS: In the demographic study, significant results were found in BMI, waist, hip, history of hyperlipidemia, and sedentary life status in male group, and significant results were found in BMI, waist, hip, and hypertension history in female group. Variant rs11189312 was found to be a novel variant affecting ZFYVE27 expressed in skeletal muscles, suggesting that rs11189312 might be related to sarcopenia as a novel discovery of this study. Further study is needed to determine the association between sarcopenia and ZFYVE27 known to be associated with spastic paraplegia.