Dataset Information

Epigenome-Wide Association Study of Dietary Fiber Intake in African American Adolescents.

ABSTRACT: SCOPE:Low fiber intake is associated with increased risk for cardiovascular disease (CVD) and cancer. However, the underlying mechanisms are not well understood. Two hypotheses are tested: 1) dietary fiber would be associated with DNA methylation levels; 2) those DNA methylation changes would be associated with visceral adiposity and inflammation. Also the possibility that the associations between fiber and DNA methylation levels might be confounded with folic acid intake as sensitivity analysis are explored. METHODS AND RESULTS:An epigenome-wide association study is conducted using Illumina 450K Bead-Chip on leukocyte DNA in 284 African American adolescents. Linear regression is performed to identify differentially methylated CpG sites associated with fiber. The methylation levels of 3 CpG sites (cg15200711, cg19462022, and cg07035602) in LPCAT1 and RASA3 genes are associated with fiber (false discovery rate [FDR] < 0.05) after adjustment for covariates including folic acid. The methylation levels of cg07035602 and cg19462022 are also associated with visceral adiposity and inflammation. CONCLUSIONS:The data show that DNA methylation levels at LPCAT1 and RASA3 genes are associated with dietary fiber intake as well as with adiposity and inflammation. Future studies are warranted to determine whether epigenetic regulation may underlie the beneficial effects of fiber intake on adiposity and inflammation.

SUBMITTER: Chen L

PROVIDER: S-EPMC6344930 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Epigenome-Wide Association Study of Dietary Fiber Intake in African American Adolescents.

Chen Li L Dong Yanbin Y Wang Xiaoling X Hao Guang G Huang Ying Y Gutin Bernard B Zhu Haidong H

Molecular nutrition & food research 20180528 12

<h4>Scope</h4>Low fiber intake is associated with increased risk for cardiovascular disease (CVD) and cancer. However, the underlying mechanisms are not well understood. Two hypotheses are tested: 1) dietary fiber would be associated with DNA methylation levels; 2) those DNA methylation changes would be associated with visceral adiposity and inflammation. Also the possibility that the associations between fiber and DNA methylation levels might be confounded with folic acid intake as sensitivity ...[more]

PMID: 29644791

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Project description:BackgroundDietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS).ResultsDNA methylation levels were measured in whole blood from the population-based KORA FF4 study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed. Below the Bonferroni correction threshold (p < 7.17 × 10-8), we identified two differentially methylated positions (DMPs) associated with PUFA intake in the KORA study. The DMP cg19937480, annotated to gene PRDX1, was positively associated with docosahexaenoic acid (DHA) in model 1 (beta: 2.00 × 10-5, 95%CI: 1.28 × 10-5-2.73 × 10-5, P value: 6.98 × 10-8), while cg05041783, annotated to gene MARK2, was positively associated with docosapentaenoic acid (DPA) in our fully adjusted model (beta: 9.80 × 10-5, 95%CI: 6.25 × 10-5-1.33 × 10-4, P value: 6.75 × 10-8). In the meta-analysis, we identified the CpG site (cg15951061), annotated to gene CDCA7L below Bonferroni correction (1.23 × 10-7) associated with eicosapentaenoic acid (EPA) intake in model 1 (beta: 2.00 × 10-5, 95% CI: 1.27 × 10-5-2.73 × 10-5, P value = 5.99 × 10-8) and we confirmed the association of cg19937480 with DHA in both models 1 and 2 (beta: 2.07 × 10-5, 95% CI: 1.31 × 10-5-2.83 × 10-5, P value = 1.00 × 10-7 and beta: 2.19 × 10-5, 95% CI: 1.41 × 10-5-2.97 × 10-5, P value = 5.91 × 10-8 respectively).ConclusionsOur study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.

Project description:BackgroundAfrican Americans have a high risk for type 2 diabetes (T2D) and insulin resistance. Studies among other population groups have identified DNA methylation loci associated with insulin resistance, but data in African Americans are lacking. Using DNA methylation profiles of blood samples obtained from the Illumina Infinium® HumanMethylation450 BeadChip, we performed an epigenome-wide association study to identify DNA methylation loci associated with insulin resistance among 136 non-diabetic, unrelated African American men (mean age 41.6 years) from the Howard University Family Study.ResultsWe identified three differentially methylated positions (DMPs) for homeostatic model assessment of insulin resistance (HOMA-IR) at 5% FDR. One DMP (cg14013695, HOXA5) is a known locus among Mexican Americans, while the other two DMPs are novel-cg00456326 (OSR1; beta = 0.027) and cg20259981 (ST18; beta = 0.010). Although the cg00456326 DMP is novel, the OSR1 gene has previously been found associated with both insulin resistance and T2D in Europeans. The genes HOXA5 and ST18 have been implicated in biological processes relevant to insulin resistance. Differential methylation at the significant HOXA5 and OSR1 DMPs is associated with differences in gene expression in the iMETHYL database. Analysis of differentially methylated regions (DMRs) did not identify any epigenome-wide DMRs for HOMA-IR. We tested transferability of HOMA-IR associated DMPs from five previous EWAS in Mexican Americans, Indian Asians, Europeans, and European ancestry Americans. Out of the 730 previously reported HOMA-IR DMPs, 47 (6.4%) were associated with HOMA-IR in this cohort of African Americans.ConclusionsThe findings from our study suggest substantial differences in DNA methylation patterns associated with insulin resistance across populations. Two of the DMPs we identified in African Americans have not been reported in other populations, and we found low transferability of HOMA-IR DMPs reported in other populations in African Americans. More work in African-ancestry populations is needed to confirm our findings as well as functional analyses to understand how such DNA methylation alterations contribute to T2D pathology.

Project description:There is growing interest in the hypertriglyceridemic waist (HTGW) phenotype, defined as high waist circumference (?95 cm in males and ?80 cm in females) combined with high serum triglyceride concentration (?2.0 mmol/L in males and ?1.5 mmol/L in females) as a marker of type 2 diabetes (T2D) and cardiovascular disease. However, the prevalence of this phenotype in high-risk populations, its association with T2D, and the genetic or epigenetic influences on HTGW are not well explored. Using data from large, extended families of Mexican Americans (a high-risk minority population in the USA) we aimed to: (1) estimate the prevalence of this phenotype, (2) test its association with T2D and related traits, and (3) dissect out the genetic and epigenetic associations with this phenotype using genome-wide and epigenome-wide studies, respectively.Data for this study was from 850 Mexican American participants (representing 39 families) recruited under the ongoing San Antonio Family Heart Study, 26 % of these individuals had HTGW. This phenotype was significantly heritable (h (2) r?=?0.52, p?=?1.1?×?10(-5)) and independently associated with T2D as well as fasting glucose levels and insulin resistance. We conducted genome-wide association analyses using 759,809 single nucleotide polymorphisms (SNPs) and epigenome-wide association analyses using 457,331 CpG sites. There was no evidence of any SNP associated with HTGW at the genome-wide level but two CpG sites (cg00574958 and cg17058475) in CPT1A and one CpG site (cg06500161) in ABCG1 were significantly associated with HTGW and remained significant after adjusting for the closely related components of metabolic syndrome. CPT1A holds a cardinal position in the metabolism of long-chain fatty acids while ABCG1 plays a role in triglyceride metabolism.Our results reemphasize the value of HTGW as a marker of T2D. This phenotype shows association with DNA methylation within CPT1A and ABCG1, genes involved in fatty acid and triglyceride metabolism. Our results underscore the importance of epigenetics in a clinically informative phenotype.

Project description:BackgroundCurrent dietary guidelines recommend that dietary fat should comprise 20-35% percent of total energy intake, with less than 10% of energy from saturated fat. However, many Americans exceed these goals and data suggest that African Americans tend to consume a higher percentage of energy from dietary fat than Whites. Because diets low in dietary fat, particularly saturated fat, are associated with lower risk for many chronic illnesses, it is important to identify strategies to reduce high fat intakes. This study examined associations of psychosocial factors with dietary fat intake in African American adults 18 to 70 years.MethodsData are self-reported from a cross-sectional survey of African Americans (n = 658) using an 11-page questionnaire, collected from June to October 2003. Associations of psychosocial (predisposing, reinforcing, and enabling) factors based on the PRECEDE framework, dietary fat-related behaviors, and participant characteristics (e.g., age, sex, education, BMI) with total and saturated fat consumption are described using linear regression and analysis of variance.ResultsThe mean age of participants was 43.9 years, 57% were female, 37% were college graduates, and 76% were overweight/obese. Respondents with lower fat intakes were female, older, had high education and very good/excellent perceived health. Among the psychosocial factors, the strongest (inverse) associations with fat intake were with two predisposing factors: belief in the importance of a low-fat diet (both genders) and high self-efficacy (women only). Fat intake was also significantly lower among participants who could count on those close for encouragement to eat healthy foods (a reinforcing factor) and among men who needed more information about preparing healthy foods (an enabling factor).ConclusionDietary interventions to decrease fat intake in African American adults may benefit from incorporating predisposing factors, such as personal beliefs and self-efficacy, in their design and implementation.

Dataset Information

Epigenome-Wide Association Study of Dietary Fiber Intake in African American Adolescents.

Publications

Epigenome-Wide Association Study of Dietary Fiber Intake in African American Adolescents.

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