Table 5:

Summary of Epigenetic Studies on Extreme Weather Events and Malnutrition

Study Title	Authors (year)	Location	Population	Exposure	Epigenetic Endpoint	Key Finding(s)
Extreme Weather Events
Wildfire-related PM2.5 and DNA methylation: An Australian twin and family study	Xu et al. (2023)	Australia	Adult female twins and their sisters in the Australian Mammographic Density Twins and Sisters Study (AMDTSS)	Long-term exposure to wildfire-related PM2.5	DNA methylation of peripheral leukocytes analyzed with with the 450K BeadChip (EWAS and 7 metrics of global DNA methylation)	-Exposure was associated with differential methylation of 26 CpGs and 33 DMRs mapping to 47 genes, which did not overlap with non-wildfire-related air pollution results. -There was a negative, but not significant, association with wildfire PM2.5 and the 7 global methylation measures.
The Impact of Prescribed Fire versus Wildfire on the Immune and Cardiovascular Systems of Children	Prunicki et al. (2019)	Fresno, California, USA	Children aged 7-8 years	Several air pollutants comprising wildfire air pollution	Candidate gene methylation analysis of the Foxp3, IL-4, IL-10, and IFNγ genes in peripheral leukocytes	-There was increased methylation of the Foxp3 promoter region post-wildfire exposure.
Pre- and peri-natal hurricane exposure alters DNA methylation patterns in children	Kello et al. (2023)	Puerto Rico	Children who were prenatally exposed to Hurricane Maria or conceived within 3 months post-disaster: Project HELiOS (Hurricane Exposures and Long-term Infant Outcomes Study)	Hurricane Maria	DNA methylation of peripheral leukocytes analyzed with with the EPIC BeadChip (EWAS)	-There was differential methylation of 47 CpGs: several hypermethylated sites associated with stage of gestation at the time of hurricane impact (biggest differences at 20-25 weeks gestation). -One significant DMR was found in association with the timing of the hurricane and annotates to the LLRC39 gene.
Malnutrition
Obesity-Associated Vitamin D Deficiency Correlates with Adipose Tissue DNA Hypomethylation, Inflammation, and Vascular Dysfunction	Mirza et al. (2022)	Chicago, Illinois, USA	Premenopausal women with obesity	Vitamin D deficiency	Global DNA methylation in adipose tissue samples measured with the 5-mC DNA kit and targeted methylation analysis of 94 inflammatory genes with the EpiTect Methyl II PCR Array	-There was decreased global DNA methylation associated with Vitamin D deficiency. -More severe Vitamin D deficiency was associated with greater hypomethylation of the promoters of the majority (70%) of inflammatory genes in the array.
Vitamin D supplementation is associated with slower epigenetic aging	Vetter et al. (2022)	Berlin, Germany	Adults in the Berlin Aging Study II (BASE-II) and GendAge study	Vitamin D supplementation	5 epigenetic clocks: 7-CpG, Horvath, Hannum, PhenoAge, and GrimAge	-Treatment with Vitamin D supplementation in deficient individuals was associated with 2.6 year lower 7-CpG age acceleration and 1.3 year lower Horvath age acceleration.
DNA methylation profile of a rural cohort exposed to early-adversity and malnutrition: An exploratory analysis	Gomez-Verjan et al. (2022)	Tlaltizapan, Mexico	Adults who experienced malnutrition and adversity early in life and healthy middle-class elders as controls	Early-life malnutrition and adversity in a rural region	DNA methylation of peripheral leukocytes analyzed with with the EPIC BeadChip (EWAS) and 4 epigenetic clocks: Horvath, Hannum, PhenoAge, and GrimAge	-Early-life malnutrition and adversity was associated with 160 hypermethylated CpG sites and 55 hypomethylated CpG sites, many of which pertain to metabolic and neurocognitive pathways. -There were differential epigenetic aging profiles based on malnutrition exposure.
Childhood exposure to hunger: associations with health outcomes in later life and epigenetic markers	Perna et al. (2020)	Saarland, Germany	Adults who experienced hunger during the German famine (1945-1948) earlier in life who are part of the ESTHER cohort	Early-life exposure to hunger	DNA methylation of peripheral leukocytes analyzed with with the 450K BeadChip (EWAS)	-While 12 CpGs had a raw p-value <0.05 associated with childhood hunger, no CpGs achieved epigenome-wide significance after multiple testing correction.
Early-life exposure to severe famine is associated with higher methylation level in the IGF2 gene and higher total cholesterol in late adulthood: the Genomic Research of the Chinese Famine (GRECF) study	Shen et al. (2019)	Anhui and Jiangxi, China	Adults in the Genomic Research of the Chinese Famine (GRECF) study who experienced the famine while an infant/fetus and those born afterwards	Chinese Great Famine in 1959-1961	Candidate gene methylation analysis of the IGF2 gene in peripheral leukocytes in blood	-There was a positive association between famine exposure and DNA methylation of the CpG1 site of the IGF2 gene and IGF2 DMR. -Each unit increase in methylation of the CpG1 site was associated with a 1.09 unit increase in total serum cholesterol levels.
DNA methylation signatures link prenatal famine exposure to growth and metabolism	Tobi et al. (2014)	The Netherlands	Adults who experienced hunger during the Hunger Winter (1944-1945) earlier in life	Prenatal exposure to hunger during the Hunger Winter	Testing of differential methylation of 28 genomic annotations in whole blood samples	-181 regions were identified as prenatal malnutrition-associated DMRs, most of which were hypermethylated, occurred in gene bodies, and displayed intermediate DNA methylation levels. -There were differences in methylation patterns based on gestational timing of exposure.