An Epigenome-Wide Association Study of Obesity-Related Traits

Abstract

We conducted an epigenome-wide association study on obesity-related traits. We used data from two prospective, population-based cohort studies: the Rotterdam Study (RS) (2006-2013) and the Atherosclerosis Risk in Communities (ARIC) Study (1990-1992). We used RS (n = 1,454) as the discovery panel and ARIC (n = 2,097) as replication panel. Linear mixed-effect models were used to assess the cross-sectional association between genome-wide DNA methylation in leukocytes with body mass index (BMI) and waist circumference (WC) adjusting for sex, age, smoking, leukocyte proportions, array number and position on array. The two latter were modelled as random effects. Fourteen CpGs were associated with BMI and 26 CpGs with WC in RS after Bonferroni-correction (P < 1.07 × 10-7), of which 12 and 13 CpGs replicated in ARIC Study, respectively. The most significant novel CpGs were located at MSI2 (cg21139312) and LARS2 (cg18030453) and were associated both with BMI and WC. CpGs at BRDT, PSMD1, IFI44L, MAP1A, and MAP3K5 were associated with BMI. CpGs at LGALS3BP, MAP2K3, DHCR24, CPSF4L, and TMEM49 were associated with WC. We report novel associations of methylation at MSI2 and LARS2 with obesity-related traits. These results provide further insight in mechanisms underlying obesity-related traits, which can enable identification of new biomarkers in obesity-related chronic diseases.

Elevated serum levels of galectin-3 binding protein is associated with insulin resistance in non-diabeteic women after menopause

“…Our results consistently indicated that a higher level of Gal-3BP was associated with increased insulin resistance. This finding was in line with data from previous in vivo and in vitro studies that showed increased expression of Gal-3BP in different phenotypes of metabolic syndrome, including nonalcoholic fatty liver disease, obesity and silent atherosclerosis [16,17]. However, in contrast to some previous studies, our data failed to show a significant correlation between Gal-3BP and clinical lipid profiles or age in women after menopause [9,18].…”

Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation

“…MSI2 participates in the IL-6, TGF-b, eukaryotic initiation factor 2, hepatocyte growth factor, and epidermal growth factor signaling pathways. 18,19 Recent blood EWASs have reported associations between MSI2 methylation with diabetes-20 and obesity-related traits, 21 which are suggested to contribute to allergic diseases. 22 ACOT7 is upregulated by lipopolysaccharide and modifies prostaglandin D2 and E2 biosynthesis.…”

Objectives, design and main findings until 2020 from the Rotterdam Study

“…We observed that a more plant-based diet and a lower intake of animal protein are associated with lower insulin resistance over time and lower risk of diabetes, independent of other lifestyle and dietary factors [205,389]. In other analyses we studied several pathways that may link nutrition or physical activity to diabetes risk and metabolic health, such as adiposity [390], inflammatory pathways [391,199] or DNA methylation [392][393][394][395].…”