Genome-wide DNA methylation analysis of pulmonary function in middle and old-aged Chinese monozygotic twins

Wang, Tong; Wang, Weijing; Li, Weilong; Duan, Haiping; Xu, Chunsheng; Tian, Xiaocao; Zhang, Dongfeng

doi:10.1186/s12931-021-01896-5

Cited by 10 publications

(8 citation statements)

References 110 publications

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“…The primary materials and methods of this study were in accord with those reported in our previously published studies (Wang, Li et al, 2023; Wang, Yao, Li et al, 2023; Wang, Yao, Tan et al, 2023).…”

Section: Methodsmentioning

confidence: 77%

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins

Yao,

Ning,

Wang

et al. 2024

Twin Res Hum Genet

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Obesity is an established risk factor for hypertension, but the mechanisms are only partially understood. We examined whether body mass index (BMI)-related DNA methylation (DNAm) variation would mediate the association of BMI with blood pressure (BP). We first conducted a genomewide DNA methylation analysis in monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediating effect of DNAm on the relationship between BMI and BP levels using the causal inference test (CIT) method and mediation analysis. Ontology enrichment analysis was performed for CpGs using the GREAT tool. A total of 60 twin pairs for BMI and systolic blood pressure (SBP) and 58 twin pairs for BMI and diastolic blood pressure (DBP) were included. BMI was positively associated with SBP (β = 1.86, p = .0004). The association between BMI and DNAm of 85 CpGs reached p < 1×10–4 level. Eleven BMI-related differentially methylated regions (DMRs) within LNCPRESS1, OGDHL, RNU1-44P, NPHS1, ECEL1P2, LLGL2, RNY4P15, MOGAT3, PHACTR3, and BAI2 were found. Of the 85 CpGs, 9 mapped to C10orf71-AS1, NDUFB5P1, KRT80, BAI2, ABCA2, PEX11G and FGF4 were significantly associated with SBP levels. Of the 9 CpGs, 2 within ABCA2 negatively mediated the association between BMI and SBP, with a mediating effect of −0.24 (95% CI [−0.65, −0.01]). BMI was also positively associated with DBP (β = 0.60, p = .0495). The association between BMI and DNAm of 193 CpGs reached p < 1×10−4 level. Twenty-five BMI-related DMRs within OGDHL, POU4F2, ECEL1P2, TTC6, SMPD4, EP400, TUBA1C and AGAP2 were found. Of the 193 CpGs, 33 mapped to ABCA2, ADORA2B, CTNNBIP1, KDM4B, NAA60, RSPH6A, SLC25A19 and STIL were significantly associated with DBP levels. Of the 33 CpGs, 12 within ABCA2, SLC25A19, KDM4B, PTPRN2, DNASE1, TFCP2L1, LMNB2 and C10orf71-AS1 negatively mediated the association between BMI and DBP, with a total mediation effect of −0.66 (95% CI [−1.07, −0.30]). Interestingly, BMI might also negatively mediate the association between the DNAm of most CpG mediators mentioned above and BP. The mediating effect of DNAm was also found when stratified by sex. In conclusion, DNAm variation may partially negatively mediate the association of BMI with BP. Our findings may provide new clues to further elucidate the pathogenesis of obesity to hypertension and identify new diagnostic biomarkers and therapeutic targets for hypertension.

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Section: Methodsmentioning

confidence: 77%

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins

Yao,

Ning,

Wang

et al. 2024

Twin Res Hum Genet

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“…Participants were excluded if they suffered from stroke, cardiovascular disease, and/or tumor, or were unable to complete the examination. Twin pairs with intra-pair HGS difference ≥0.1 kg were chosen for the trait-discordant monozygotic twin design based on our previous experience with similar studies ( Wang W. et al, 2021 ; Wang T. et al, 2021 ; Wang et al, 2023 ). A total of 66 HGS-discordant monozygotic twin pairs were included.…”

Section: Methodsmentioning

confidence: 99%

“…CpGs with an average methylation β -value below 0.01 or those with more than 10 missing observations were excluded. The methylation β -values were transformed to M-values by log 2 transformation ( Wang T. et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins

Luo,

Wang,

et al. 2024

Front. Cell Dev. Biol.

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Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins.Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents.Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population.Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline.

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“…The primary materials and methods used in this study were in accordance with those of our previously published studies [ 24 – 29 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of key DNA methylation changes on fasting plasma glucose: a genome-wide DNA methylation analysis in Chinese monozygotic twins

Wang

Yao

Tan

et al. 2023

Diabetol Metab Syndr

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Background Elevated fasting plasma glucose (FPG) levels can increase morbidity and mortality even when it is below the diagnostic threshold of type 2 diabetes mellitus (T2DM). We conducted a genome-wide DNA methylation analysis to detect DNA methylation (DNAm) variants potentially related to FPG in Chinese monozygotic twins. Methods Genome-wide DNA methylation profiling in whole blood of twins was performed using Reduced Representation Bisulfite Sequencing (RRBS), yielding 551,447 raw CpGs. Association between DNAm of single CpG and FPG was tested using a generalized estimation equation. Differentially methylated regions (DMRs) were identified using comb-P approach. ICE FALCON method was utilized to perform the causal inference. Candidate CpGs were quantified and validated using Sequenom MassARRAY platform in a community population. Weighted gene co-expression network analysis (WGCNA) was conducted using gene expression data from twins. Results The mean age of 52 twin pairs was 52 years (SD: 7). The relationship between DNAm of 142 CpGs and FPG reached the genome-wide significance level. Thirty-two DMRs within 24 genes were identified, including TLCD1, MRPS31P5, CASZ1, and CXADRP3. The causal relationship of top CpGs mapped to TLCD1, MZF1, PTPRN2, SLC6A18, ASTN2, IQCA1, GRIN1, and PDE2A genes with FPG were further identified using ICE FALCON method. Pathways potentially related to FPG were also identified, such as phospholipid-hydroperoxide glutathione peroxidase activity and mitogen-activated protein kinase p38 binding. Three CpGs mapped to SLC6A18 gene were validated in a community population, with a hypermethylated direction in diabetic patients. The expression levels of 18 genes (including SLC6A18 and TLCD1) were positively correlated with FPG levels. Conclusions We detect many DNAm variants that may be associated with FPG in whole blood, particularly the loci within SLC6A18 gene. Our findings provide important reference for the epigenetic regulation of elevated FPG levels and diabetes.

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Genome-wide DNA methylation analysis of pulmonary function in middle and old-aged Chinese monozygotic twins

Cited by 10 publications

References 110 publications

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins

Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins

Identification of key DNA methylation changes on fasting plasma glucose: a genome-wide DNA methylation analysis in Chinese monozygotic twins

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