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Genome- and epigenome-wide association studies identify susceptibility of CpG sites and regions for metabolic syndrome in a Korean population.
Lee, Ho-Sun; Kim, Boram; Park, Taesung.
Afiliação
  • Lee HS; Forensic Toxicology Division, Daegu Institute, National Forensic Service, Chilgok-gun, 39872, Gyeongsangbuk-do, Korea. hs4369@gmail.com.
  • Kim B; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea. hs4369@gmail.com.
  • Park T; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Korea.
Clin Epigenetics ; 16(1): 60, 2024 Apr 29.
Article em En | MEDLINE | ID: mdl-38685121
ABSTRACT

BACKGROUND:

While multiple studies have investigated the relationship between metabolic syndrome (MetS) and its related traits (fasting glucose, triglyceride, HDL cholesterol, blood pressure, waist circumference) and DNA methylation, our understanding of the epigenetic mechanisms in MetS remains limited. Therefore, we performed an epigenome-wide meta-analysis of blood DNA methylation to identify differentially methylated probes (DMPs) and differentially methylated regions (DMRs) associated with MetS and its components using two independent cohorts comprising a total of 2,334 participants. We also investigated the specific genetic effects on DNA methylation, identified methylation quantitative trait loci (meQTLs) through genome-wide association studies and further utilized Mendelian randomization (MR) to assess how these meQTLs subsequently influence MetS status.

RESULTS:

We identified 40 DMPs and 27 DMRs that are significantly associated with MetS. In addition, we identified many novel DMPs and DMRs underlying inflammatory and steroid hormonal processes. The most significant associations were observed in 3 DMPs (cg19693031, cg26974062, cg02988288) and a DMR (chr1145440444-145441553) at the TXNIP, which are involved in lipid metabolism. These CpG sites were identified as coregulators of DNA methylation in MetS, TG and FAG levels. We identified a total of 144 cis-meQTLs, out of which only 13 were found to be associated with DMPs for MetS. Among these, we confirmed the identified causal mediators of genetic effects at CpG sites cg01881899 at ABCG1 and cg00021659 at the TANK genes for MetS.

CONCLUSIONS:

This study observed whether specific CpGs and methylated regions act independently or are influenced by genetic effects for MetS and its components in the Korean population. These associations between the identified DNA methylation and MetS, along with its individual components, may serve as promising targets for the development of preventive interventions for MetS.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhas de CpG / Metilação de DNA / Predisposição Genética para Doença / Síndrome Metabólica / Locos de Características Quantitativas / Epigênese Genética / Estudo de Associação Genômica Ampla Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: Clin Epigenetics Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhas de CpG / Metilação de DNA / Predisposição Genética para Doença / Síndrome Metabólica / Locos de Características Quantitativas / Epigênese Genética / Estudo de Associação Genômica Ampla Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: Clin Epigenetics Ano de publicação: 2024 Tipo de documento: Article