Abstract P205: Genome-Wide Epigenetic Study of Prenatal Famine Exposure and Blood Lipids in Late Adulthood: The Genomic Research of the Chinese Great Famine (GRECF) Study

Abstract

Objectives: To identify differentially methylated DNA positions associated with prenatal exposure to the Chinese Great Famine and their influence on blood lipids in late adulthood among participants of the Genomic Research of the Chinese Great Famine (GRECF) study. Methods: The GRECF study was designed to study the influence of the Chinese Great Famine on human genome and metabolic disorders. We randomly selected 8 participants born in a famine stricken area during the Great Chinese Famine (1959-1961) and 8 sex- and residency of location-matched participants born within 3 years after the famine. Genome-wide DNA methylation was profiled using the IlluminaEPIC BeadChip. After quality control, a total of 391,633 probes remained for analyses. Total cholesterol, low-density lipoprotein cholesterol (LDLC), and high-density lipoprotein cholesterol (HDLC) were assayed using enzymatic colormetric tests. Beta values for each probe were compared between individuals with and without famine exposure using the empirical Bayes statistics implemented in Limma software. Probes with a raw p-value <0.05 were mapped to genes using Kobas followed by KEGG pathway enrichment analyses. Those probes were also evaluated for associations with blood lipids using linear regression. False discovery rate (FDR) method was applied to correct for multiple testing. Results: A total of 48,055 CpG positions showed nominal associations ( p <0.05) with prenatal famine exposure. None of them was significant after FDR correction. The top seven CpG positions reached p <1х10 -5 and are relevant to metabolism and/or development. Specifically, prenatal famine exposure was associated increased methylation levels in CpG positions in C8orf31 , ELAVL1 , and U6 and decreased methylation levels in CpG positions in GBA2 , SHOX2 , SLC1A4 , and NPHP4 . Of note, the CpG probe in the GBA2 gene lies in the first exonic region. Pathway enrichment analyses to genes harboring nominally significant probes revealed 44 KEGG pathways that were significant after FDR correction ( q <0.05), of which, 17 pathways are related to metabolism, development, and/or energy expenditure, including 11 pathways of the EGFR, FGFR, and SCF/KIT signaling and pathways of gene expression ( p =1.2х10 -11 ), metabolism ( p =6.8х10 -11 ), developmental biology ( p =7.9х10 -8 ), metabolism of protein ( p =3.1х10 -7 ), and metabolism of lipids and lipoproteins ( p =1.3х10 -4 ). None of the 48,055 probes were associated with blood lipid traits after FDR correction, however, four probes had p-values<1.0х10 -4 for associations with LDLC or HDLC. The four probes lie in ZC3H18 , LINC00243 , PIGQ , and HS3ST4 genes, of which, PIGQ plays an important role in lipid metabolism. Conclusion: The small-scale genome-wide epigenetic study revealed important epigenetic changes associated with both prenatal famine exposure and blood lipids in late adulthood.