Genome-Wide Analysis of DNA Methylation Signatures Linking Prenatal Exposure to the Chinese Great Famine and Blood Lipids in Late Adulthood: The Genomic Research of the Chinese Famine (GRECF) Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Prenatal Famine Assessment
2.3. DNA Methylation Measurements
2.4. Blood Lipid Measurements
2.5. Anthropometric Measurements
2.6. Statistical Analyses
3. Results
3.1. EWAS Results for Prenatal Famine Exposure
3.2. Replication of Previous Reported DNAm Changes Associated with Famine
3.3. Enrichment Analysis
3.4. Associations of DNAm with Blood Lipids
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Chr | chromosome |
CI | confidence intervals |
CpG | 5’-C-phosphate-G-3’ |
EWAS | epigenome-wide association study |
FDR | false discovery rate |
GRECF | the genomic research of the Chinese famine |
HDL-C | high-density lipoprotein cholesterol |
HSV-1 | herpes simplex virus type 1 |
ICR | imprint control region |
LDL-C | low-density lipoprotein cholesterol |
POS | position |
SE | standard error |
TC | total cholesterol |
TSS | transcription start site |
UTR | untranslated region |
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Probe ID | Chr: POS (Build 37) | Site Function | Nearest Genes | Beta Values | p Values | |
---|---|---|---|---|---|---|
Exposed Group | Matched Control | |||||
cg10360725 | 8:144139316 | 5’UTR | C8orf31 | 0.36 | 0.95 | 2.7 × 10−7 |
cg04359527 | 19:7980718 | TSS | ELAVL1 | 0.16 | 0.25 | 4.7 × 10−6 |
cg08258661 | 9:35748665 | Exon | GBA2 | 0.03 | 0.02 | 4.9 × 10−6 |
cg09542210 | 3:157821536 | Body | SHOX2 | 0.07 | 0.04 | 5.4 × 10−6 |
cg11736566 | 4:57155953 | 5’UTR | U6 | 0.87 | 0.92 | 7.5 × 10−6 |
cg02085294 | 2:65220148 | 5’UTR | SLC1A4 | 0.90 | 0.82 | 7.9 × 10−6 |
cg06173758 | 1:5957461 | Body | NPHP4 | 0.94 | 0.91 | 9.5 × 10−6 |
Terms | Pathway ID 1 | p Values | q Values |
---|---|---|---|
Pathways in cancer | hsa05200 | 7.94 × 10−6 | 3.98 × 10−3 |
Hemostasis | R-HSA-109582 | 5.00 × 10−5 | 1.94 × 10−2 |
General function | |||
Gene expression | R-HSA-74160 | 1.19 × 10−11 | 1.01 × 10−7 |
Signal transduction | R-HSA-162582 | 1.51 × 10−6 | 1.31 × 10−3 |
Disease | R-HSA-1643685 | 1.54 × 10−6 | 1.31 × 10−3 |
Generic transcription pathway | R-HSA-212436 | 2.39 × 10−6 | 1.85 × 10−3 |
Transmembrane transport of small molecules | R-HSA-382551 | 2.60 × 10−6 | 1.85 × 10−3 |
Vesicle-mediated transport | R-HSA-5653656 | 3.65 × 10−5 | 1.56 × 10−2 |
Post-translational protein modification | R-HSA-597592 | 7.44 × 10−5 | 2.35 × 10−2 |
Extracellular matrix organization | R-HSA-1474244 | 1.04 × 10−4 | 3.07 × 10−2 |
Downstream signal transduction | R-HSA-186763 | 1.06 × 10−4 | 3.07 × 10−2 |
Membrane Trafficking | R-HSA-199991 | 1.19 × 10−4 | 3.26 × 10−2 |
Cell cycle | R-HSA-1640170 | 2.77 × 10−4 | 4.69 × 10−2 |
Growth and development | |||
Developmental biology | R-HSA-1266738 | 7.91 × 10−8 | 1.69 × 10−4 |
Signaling by PDGF | R-HSA-186797 | 3.62 × 10−5 | 1.56 × 10−2 |
Signaling by EGFR | R-HSA-177929 | 6.92 × 10−5 | 2.35 × 10−2 |
Signaling by FGFR2 | R-HSA-5654738 | 1.08 × 10−4 | 3.07 × 10−2 |
Signaling by FGFR3 | R-HSA-5654741 | 1.23 × 10−4 | 3.26 × 10−2 |
Signaling by FGFR | R-HSA-190236 | 1.29 × 10−4 | 3.26 × 10−2 |
Signaling by FGFR4 | R-HSA-5654743 | 1.32 × 10−4 | 3.26 × 10−2 |
Downstream signaling of activated FGFR4 | R-HSA-5654716 | 1.63 × 10−4 | 3.42 × 10−2 |
Downstream signaling of activated FGFR2 | R-HSA-5654696 | 1.63 × 10−4 | 3.42 × 10−2 |
Downstream signaling of activated FGFR3 | R-HSA-5654708 | 1.63 × 10−4 | 3.42 × 10−2 |
Signaling by FGFR1 | R-HSA-5654736 | 1.71 × 10−4 | 3.42 × 10−2 |
Downstream signaling of activated FGFR1 | R-HSA-5654687 | 1.97 × 10−4 | 3.74 × 10−2 |
Wnt signaling pathway | P00057 | 2.08 × 10−4 | 3.86 × 10−2 |
Signaling by Wnt | R-HSA-195721 | 2.36 × 10−4 | 4.20 × 10−2 |
PI3K-Akt signaling pathway | hsa04151 | 2.41 × 10−4 | 4.20 × 10−2 |
Signaling by SCF-KIT | R-HSA-1433557 | 2.80 × 10−4 | 4.69 × 10−2 |
Immune function | |||
Immune system | R-HSA-168256 | 1.54 × 10−7 | 2.62 × 10−4 |
Adaptive immune system | R-HSA-1280218 | 4.73 × 10−6 | 2.69 × 10−3 |
Fc epsilon receptor (FCERI) signaling | R-HSA-2454202 | 7.24 × 10−5 | 2.35 × 10−2 |
DAP12 interactions | R-HSA-2172127 | 1.74 × 10−4 | 3.42 × 10−2 |
Innate immune system | R-HSA-168249 | 1.74 × 10−4 | 3.42 × 10−2 |
DAP12 signaling | R-HSA-2424491 | 2.17 × 10−4 | 3.94 × 10−2 |
Metabolism | |||
Metabolism | R-HSA-1430728 | 6.76 × 10−11 | 2.88 × 10−7 |
Metabolism of proteins | R-HSA-392499 | 3.14 × 10−7 | 3.82 × 10−4 |
Metabolic pathways | hsa01100 | 2.92 × 10−6 | 1.91 × 10−3 |
Metabolism of lipids and lipoproteins | R-HSA-556833 | 1.34 × 10−4 | 3.26 × 10−2 |
Nervous system | |||
Axon guidance | R-HSA-422475 | 7.89 × 10−7 | 8.41 × 10−4 |
Neuronal system | R-HSA-112316 | 3.49 × 10−6 | 2.12 × 10−3 |
Signaling by NGF | R-HSA-166520 | 6.07 × 10−6 | 3.23 × 10−3 |
NGF signaling via TRKA from the plasma membrane | R-HSA-187037 | 3.34 × 10−5 | 1.56 × 10−2 |
Probe ID | Pathway | Position | Nearest Gene | Function | β (SE) | p Values | q Values 1 |
---|---|---|---|---|---|---|---|
High-density lipoprotein cholesterol | |||||||
cg01421548 | >R-HSA-1430728 | >16:25705355 | > HS3ST4 | >Body | >5.7 (1.0) | >5.23 × 10−5 | >0.04 |
Low-density lipoprotein cholesterol | |||||||
cg02622866 | hsa04151 | 2:176032527 | ATF2 | 5’UTR | −140.7 (34.4) | 1.09 × 10−3 | 0.03 |
cg01105385 | hsa04151 | 5:67584222 | PIK3R1 | Body | 65.0 (17.1) | 1.94 × 10−3 | 0.03 |
cg07316730 | hsa04151 | 17:73316721 | GRB2 | Body | 41.7 (10.4) | 1.32 × 10−3 | 0.03 |
>cg09180702 | >R-HSA-1430728 | >16:633722 | > PIGQ | >3’UTR | >−6.9 (1.3) | >9.21 × 10−5 | >0.04 |
Log triglycerides | |||||||
cg08460387 | R-HSA-5653656 | 1:26000291 | MAN1C1 | Body | 51.6 (9.7) | 1.09 × 10−4 | 0.02 |
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Wang, H.; Shen, L.; Liu, T.; Zhang, R.; Wang, Z.; Wei, J.; Shen, Y.; Guo, J.; Miles, T.; Li, C.; et al. Genome-Wide Analysis of DNA Methylation Signatures Linking Prenatal Exposure to the Chinese Great Famine and Blood Lipids in Late Adulthood: The Genomic Research of the Chinese Famine (GRECF) Study. Nutrients 2025, 17, 3147. https://doi.org/10.3390/nu17193147
Wang H, Shen L, Liu T, Zhang R, Wang Z, Wei J, Shen Y, Guo J, Miles T, Li C, et al. Genome-Wide Analysis of DNA Methylation Signatures Linking Prenatal Exposure to the Chinese Great Famine and Blood Lipids in Late Adulthood: The Genomic Research of the Chinese Famine (GRECF) Study. Nutrients. 2025; 17(19):3147. https://doi.org/10.3390/nu17193147
Chicago/Turabian StyleWang, Huan, Luqi Shen, Tingting Liu, Ruiyuan Zhang, Zhenghe Wang, Jingkai Wei, Ye Shen, Jinzhen Guo, Toni Miles, Changwei Li, and et al. 2025. "Genome-Wide Analysis of DNA Methylation Signatures Linking Prenatal Exposure to the Chinese Great Famine and Blood Lipids in Late Adulthood: The Genomic Research of the Chinese Famine (GRECF) Study" Nutrients 17, no. 19: 3147. https://doi.org/10.3390/nu17193147
APA StyleWang, H., Shen, L., Liu, T., Zhang, R., Wang, Z., Wei, J., Shen, Y., Guo, J., Miles, T., Li, C., & Zou, Z. (2025). Genome-Wide Analysis of DNA Methylation Signatures Linking Prenatal Exposure to the Chinese Great Famine and Blood Lipids in Late Adulthood: The Genomic Research of the Chinese Famine (GRECF) Study. Nutrients, 17(19), 3147. https://doi.org/10.3390/nu17193147