J Korean Med Sci.  2022 Dec;37(50):e346. 10.3346/jkms.2022.37.e346.

Demographic and Genome Wide Association Analyses According to Muscle Mass Using Data of the Korean Genome and Epidemiology Study

• Gim JA
• Lee S
• Kim SC
• Baek KW
• Yoo JI

• KMID: 2537049
• DOI: http://doi.org/10.3346/jkms.2022.37.e346

Abstract

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.

Keyword

Skeletal Muscle; Korean Genome and Epidemiology Study; Single Nucleotide Polymorphisms; Genome-Wide Association Studies; ZFYVE27

Figure

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  Fig. 1 Manhattan plot of each group classified by gender. (A) Manhattan plot in the men group, (B) Manhattan plot in the women group.

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  Fig. 2 Q-Q plot of each group classified by gender. (A) Q-Q plot in the men group. (B) Q-Q plot in the women group.Q-Q = Quantile-Quantile.

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  Fig. 3 Interactive heatmap matrix of pairwise linkage disequilibrium statistics in rs11189312 and ZFYVE27 associated SNPs. (A) All pairwise R square statistics. (B) All pairwise D prime statistics. (C) Interactive heat map of associated SNPs.SNP = single nucleotide polymorphism.

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