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  • 1
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    Abstract P356: The Temporal Relationship Between Body Mass Index and DNA Methylation: Longitudinal Epigenome-Wide Association From the Bogalusa Heart Study
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Vol. 131, No. suppl_1 ( 2015-03-10)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 131, No. suppl_1 ( 2015-03-10)
    Abstract: Obesity, as a metabolic disorder, can be either a cause or consequence of epigenetic alterations, but their temporal relationship is unknown. This study assessed the hypothesis that BMI and DNA methylation changes mutually influence each other, dependent on different methylation sites in the human genome. Peripheral leukocyte DNA methylation data on 294,840 CpG sites filtered from 485,577 sites generated by Illumina 450K BeadChip were analyzed in two discovery cohorts (585 whites and 245 blacks) and a longitudinal cohort (95 whites and 43 blacks followed 3.2 years) in the Bogalusa Heart Study (BHS) and 2 replication cohorts (450 twins in Chinese National Twin Study, 456 blacks in Georgia Prevention Institute Epigenetics of Obesity Study). BMI was significantly associated with methylation levels at cg17260706 (negatively), cg13562284 (negatively) and cg15721584 (positively) consistently in the discovery cohorts, and these associations were replicated in both 450 Chinese twins and 456 blacks in the same directions. The temporal relationship analyses in a cross-lagged path analysis model showed a one-directional relation from BMI to methylation changes at cg17260706 in BCL9L gene in both races as seen in the figure. The temporal relationship was different in blacks versus whites for the other two CpGs. In longitudinal analysis of BMI measured 4 or more times over 40 years in the BHS, childhood (p 〈 0.05) and adulthood BMI (p 〈 0.01) and its long-term burden (p 〈 0.01) and increasing trend (p 〈 0.01) were all negatively associated with the methylation level at cg17260706 in 615 whites and 276 blacks. In addition, an SNP in the BCL9L gene (rs586763) was associated with the methylation level at cg17260706 (p 〈 0.05) in blacks only; decreasing slopes of the methylation level at cg17260706 with increasing BMI were significantly different in three genotype groups in blacks (p 〈 0.05), but not in whites. In conclusion, higher BMI results in lower methylation levels at cg17260706 in the BCL9L gene.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.131.suppl_1.p356
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 2
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    Impact of cigarette smoking on the relationship between body mass index and insulin: L ongitudinal observation from the Bogalusa Heart Study
    Wiley ; 2018
    In:  Diabetes, Obesity and Metabolism Vol. 20, No. 7 ( 2018-07), p. 1578-1584
    Details
    In: Diabetes, Obesity and Metabolism, Wiley, Vol. 20, No. 7 ( 2018-07), p. 1578-1584
    Abstract: Despite the inverse association between cigarette smoking and body mass index (BMI), it is unknown whether the effect of smoking on insulin is mediated through decreased BMI. This study aims to examine the temporal relationship between BMI and insulin, the impact of smoking on this relationship and the mediation effect of BMI on the association between smoking and insulin levels. Methods The longitudinal cohort consisted of 1121 adults (807 white and 314 black participants, mean age, 42.0 years at follow‐up) for whom BMI and fasting insulin were measured twice, with an average follow‐up period of 17.1 years. Cross‐lagged panel and mediation analysis models were used to examine the temporal relationship between BMI and insulin, and the mediation effect of BMI on the smoking‐insulin association. Results Smoking was inversely associated with insulin (regression coefficient, −0.073; P = .015 at baseline and −0.121; P 〈 .001 at follow‐up), adjusting for age, race and gender. After additional adjustment for follow‐up periods, the cross‐lagged path coefficient from BMI to insulin (β, 0.226; P 〈 .001) was significantly greater than that from insulin to BMI (β, −0.029; P = .208), with P 〈 .001 for the difference. The path coefficient from BMI to insulin was significantly greater in non‐smokers (β, 0.273; P 〈 .001) than in smokers (β, 0.122; P = .046), with P = .013 for the difference. The mediation effect of BMI on the smoking‐insulin association was estimated at 53.4% ( P = .030) at baseline and 58.7% ( P 〈 .001) at follow‐up. Conclusions These findings suggest that cigarette smoking has a significant impact on the one‐directional relationship from BMI to insulin. The insulin‐lowering effect of smoking is predominantly mediated through decreased BMI as the result of smoking.
    Type of Medium: Online Resource
    ISSN: 1462-8902 , 1463-1326
    URL: Issue
    URL: Article
    DOI: 10.1111/dom.2018.20.issue-7
    DOI: 10.1111/dom.13259
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2004918-3
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  • 3
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    Long-term Impact of Childhood Adiposity on Adult Metabolic Syndrome Is Modified by Insulin Resistance: The Bogalusa Heart Study
    Springer Science and Business Media LLC ; 2015
    In:  Scientific Reports Vol. 5, No. 1 ( 2015-12-07)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2015-12-07)
    Abstract: Childhood adiposity and insulin resistance are well-known risk factors for adult metabolic syndrome (MetS). This study aims to examine whether the association between childhood adiposity and adult MetS is modified by insulin resistance. The cohort consisted of 1,593 black and white subjects, aged 19–50 years at follow-up, who were examined 19 years apart on average as children and adults for MetS variables. The prevalence of adult MetS was compared between the insulin-sensitive obesity and insulin-resistant obesity groups in childhood. Adult MetS prevalence was higher in the insulin-resistant obesity group than in the insulin-sensitive obesity group (34.9% vs. 24.3%, p = 0.008). In multivariable logistic regression analyses adjusted for age, race, gender and follow-up years, individuals with insulin-resistant obesity in childhood were 1.7 times (p = 0.011) more likely to have MetS 19 years later on average than those with insulin-sensitive obesity in childhood. Odds ratio did not differ significantly between blacks and whites (p = 0.724). ORs for the association of childhood BMI with adult MetS significantly increased with increasing tertiles of childhood HOMA (p  〈  0.001 for trend). These findings suggest that insulin resistance amplifies the association between childhood adiposity and adult MetS and underscore the importance of preventing both adiposity and insulin resistance in early life.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/srep17885
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
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  • 4
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    Novel Metabolites Are Associated With Augmentation Index and Pulse Wave Velocity: Findings From the Bogalusa Heart Study
    Oxford University Press (OUP) ; 2019
    In:  American Journal of Hypertension Vol. 32, No. 6 ( 2019-05-09), p. 547-556
    Details
    In: American Journal of Hypertension, Oxford University Press (OUP), Vol. 32, No. 6 ( 2019-05-09), p. 547-556
    Abstract: Metabolomics study may help identify novel mechanisms underlying arterial stiffening. METHODS We performed untargeted metabolomics profiling among 1,239 participants of the Bogalusa Heart Study. After quality control, 1,202 metabolites were evaluated for associations with augmentation index (AI) and pulse wave velocity (PWV), using multivariate linear regression adjusting for age, sex, race, education, smoking, drinking, body weight, body height, physical activity, and estimated glomerular filtration rate. Heart rate, blood pressure and antihypertensive medication usage, lipids, and fasting glucose were sequentially adjusted in the sensitivity analyses for significant metabolites. Weighted correlation network analysis was applied to build metabolite networks. RESULTS Six novel metabolites were negatively associated with AI, of which, 3-methyl-2-oxobutyrate had the lowest P value and the largest effect size (β = –6.67, P = 5.99 × 10–6). Heart rate contributed to a large proportion (25%–58%) of the association for each metabolite. Twenty-one novel metabolites were identified for PWV, of which, fructose (β = 0.61, P = 6.18 × 10–10) was most significant, and histidine had the largest effect size (β = –1.09, P = 2.51 × 10–7). Blood pressure played a major contribution (9%–54%) to the association for each metabolite. Furthermore, 16 metabolites were associated with arterial stiffness independent of traditional risk factors. Network analysis identified 2 modules associated with both AI and PWV (P & lt; 8.00 × 10–4). One was composed of metabolites from the glycerolipids synthesis and recycling pathway, and the other was involved in valine, leucine, and isoleucine metabolism. One module related to sphingomyelin metabolism was associated with PWV only (P = 0.002). CONCLUSIONS This study has identified novel and important metabolites and metabolic networks associated with arterial stiffness.
    Type of Medium: Online Resource
    ISSN: 0895-7061 , 1941-7225
    URL: Article
    DOI: 10.1093/ajh/hpz046
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1479505-X
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  • 5
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    Abstract MP74: The Effect Of BMI On Metabolic Traits Is Mediated By A Novel Diabetes Marker
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 145, No. Suppl_1 ( 2022-03)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. Suppl_1 ( 2022-03)
    Abstract: Introduction: 2-aminoadipic acid (2-AAA) secreted during adipogenesis is a novel marker for diabetes. Hypothesis: 2-AAA mediates the associations between body mass index (BMI) and metabolic measures, and the effect of 2-AAA can be modified by environmental factors. Methods: We performed cross-sectional analyses among all 1,252 participants in the Bogalusa Heart Study 2016 survey. Serum 2-AAA and 110 xenobiotics were profiled through untargeted UPLC-MS/MS. Mediation effects of 2-AAA on the associations between BMI and metabolic traits were estimated by comparing the BMI-traits associations before and after controlling for 2-AAA. P value for a mediation effect was estimated by 1,000,000 times Monte-Carlo simulation. We further performed interaction analyses to identify xenobiotics that modify the effect of 2-AAA on metabolic traits. Age, sex, race, education, smoking, drinking, and use of lipid, glucose, or blood pressure lowering medications were adjusted in all analyses. Results: After Bonferroni correction, 2-AAA significantly mediated the association of BMI with high density lipoprotein cholesterol (HDLC) (beta= -0.03 mg/dL, p=1.70х10 -4 ), log transformed triglyceride (lgTG) (beta=0.002, p=1х10 -6 ), fasting glucose (beta=0.05 mg/dL, p=2.87х10 -3 ), and hemoglobin A1c (HbA1c) (beta=0.002%, p=8.50х10 -4 ). The proportions of associations explained by 2-AAA ranged from 5.12% for HDLC to 13.23% for lgTG. When stratified by race and medication usage, the mediation effects were stronger among Whites and those not taking medications (P for interaction 〈 0.05). Furthermore, 14 xenobiotics modified the associations of 2-AAA with HDLC/lgTG or glucose/HbA1c (Table), e.g., the association between 2-AAA and HbA1c was much stronger among participants with higher levels of 4-acetaminophen sulfate (P for interaction=3.03х10 -5 ), a metabolite of commonly used over-the-counter analgesics. Conclusion: 2-AAA mediated the effect of BMI on metabolic traits, and this effect was modified by environmental factors.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.145.suppl_1.MP74
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 6
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    Abstract 10959: Phenotypic Age Mediates the Effects of Life's Simple 7 on Reduced Mortality Risk in the US Adults
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Background: Phenotypic age, a newly developed marker for biological aging, improves risk prediction for adverse health events than chronological age. "Life’s Simple 7" (LS7) is a set of 7 recommended healthy lifestyle metrics proposed by the AHA to improve cardiovascular health. It is unknown, however, whether phenotypic age mediates the protective effects of healthy lifestyles on cardiovascular disease (CVD)- and all-cause mortality. Methods: Prospective analyses were performed using NHANES 1999-2010 data (6 cycles) on 9842 adults with linked death records till Dec 31, 2015. Adjusted hazard ratios (aHR) were estimated for phenotypic age, LS7-score, and LS7’s individual components for all-cause and cardiovascular mortality. Mediation analyses were performed using structural equation modeling. Results: One point increment in LS7-score was associated with a 0.92 (95% CI 0.87-0.98) year younger in phenotypic age, independent of general demographic characteristics and chronological age. During a median of 10.33-year follow-up, 1616 deaths were recorded, 323 being cardiovascular. One year increment in phenotypic age was associated with a higher risk of all-cause (aHR=1.05, 95% CI 1.04-1.05) and cardiovascular (1.04 [1.03-1.06]) mortality. The mediation analysis revealed that phenotypic age was estimated to mediate 66% and 42% of the total effects of LS7 on all-cause and cardiovascular mortality, respectively. Conclusion: Our data indicate that adherence to LS7 guidelines significantly slows down biological aging, which results in a prolonged lifespan as well as a reduced risk of cardiovascular mortality.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.10959
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 7
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    Temporal Relationship Between Childhood Body Mass Index and Insulin and Its Impact on Adult Hypertension : The Bogalusa Heart Study
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Hypertension Vol. 68, No. 3 ( 2016-09), p. 818-823
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. 3 ( 2016-09), p. 818-823
    Abstract: Although obesity and insulin resistance are closely correlated, their temporal sequences in early life and influence on adult hypertension are largely unknown. This study aims to delineate the temporal relationship patterns between body mass index (BMI) and insulin in childhood and their impact on adult hypertension. The longitudinal cohort consisted of 990 adults (630 whites and 360 blacks) who had BMI and fasting insulin measured twice 5.4 years apart in childhood (mean age, 10.5 years at baseline and 15.9 years at follow-up) and blood pressure measured 14.7 years later in adulthood (mean age, 30.5 years). Cross-lagged panel and mediation analysis models were used to examine the temporal relationship between childhood BMI and insulin and its impact on adult hypertension. After adjusting for age, race, sex, and follow-up years, the cross-lagged path coefficient (β=0.33; P 〈 0.001) from baseline BMI to follow-up insulin was significantly greater than the path coefficient (β=−0.02; P 〉 0.05) from baseline insulin to follow-up BMI in childhood with P 〈 0.001 for the difference in βs. Blacks and whites showed similar patterns of the temporal relationship. The path coefficient (β=0.59; P 〈 0.001) from BMI to insulin in the hypertensive group was significantly greater than that (β=0.24; P 〈 0.001) in normotensive group, with P 〈 0.001 for the difference in βs between these 2 groups. The mediation effect of childhood insulin on the childhood BMI–adult hypertension association was estimated at 21.1% ( P 〈 0.001). These findings provide evidence that higher BMI levels precede hyperinsulinemia during childhood, and this 1-directional relation plays a role in the development of hypertension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.116.07991
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2094210-2
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  • 8
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    Abstract P111: Untargeted Metabolomics Study And Bidirectional Mendelian Randomization Analyses Identified Novel Metabolites Mediating The Effect Of Current Smoking On Body Mass Index
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 143, No. Suppl_1 ( 2021-05-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 143, No. Suppl_1 ( 2021-05-25)
    Abstract: Introduction: Many studies identified that smokers had lower body mass index (BMI) than non-smokers, but the underlying mechanisms are not well understood. Hypothesis: An untargeted metabolomics study will identify novel mechanisms underlying smoking associated weight loss. Methods: We performed cross-sectional analyses among all 248 current smokers and 637 never smokers participated in the Bogalusa Heart Study 2016 survey. After stringent quality control and normalization, 1,202 plasma metabolites were assessed for mediation effects on smoking-BMI association after controlling for age, gender, race, education, drinking and physical activity. The collective mediation effects of metabolites were estimated by comparing the smoking-BMI associations before and after controlling for all significant metabolites after Bonferroni correction. Bidirectional Mendelian randomization analyses were then performed on a subset of participants (n=654) to delineate causal directions among smoking, BMI, and significant metabolites. We constructed multi-locus genetic risk scores (GRS) for smoking and BMI based on findings from published GWASs with a sample size of more than 250,000. Multivariable linear regression controlling for the same covariates as in the mediation analyses was used to estimate associations between smoking- and BMI-GRSs and the significant metabolites. Results: Compared to never smokers, current smokers had a 3.31 kg/m 2 (95% confidence interval [CI]: 2.15-4.47) lower BMI after adjusting for all covariables. A total of 40 metabolites significantly mediated and explained 90.7% of the smoking-BMI association. Seven of the significant metabolites were associated with smoking GRS but not BMI GRS, suggesting a true mediation role in the smoking-BMI association. The seven metabolites, including homoarginine (mediation beta=-0.49 kg/m 2 , 95% CI: -0.78 to -0.26), 1-oleoyl-GPE (18:1) (mediation beta=-0.44 kg/m 2 , 95% CI: -0.72 to -0.22), 1-linoleoyl-GPE (18:2)* (mediation beta=-0.59 kg/m 2 , 95% CI: -0.90 to -0.32), beta-cryptoxanthin (mediation beta=0.53 kg/m 2 , 95% CI: 0.27 to 0.83), 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4) (mediation beta=0.39 kg/m 2 , 95% CI: 0.18 to 0.65), sphingomyelin (d18:2/21:0, d16:2/23:0)* (mediation beta=-0.54 kg/m 2 , 95% CI: -0.84 to -0.28), and sphingomyelin (d17:2/16:0, d18:2/15:0)* (mediation beta=-0.92 kg/m 2 , 95% CI: -1.30 to -0.59), mediated 36.3% of the association between current smoking and BMI. We also identified 6 metabolites significantly associated with BMI GRS but not with smoking GRS, and 2 significantly associated with both smoking- and BMI-GRSs. Conclusions: We identified 7 plasma metabolites that mediated a large proportion of the association between smoking and BMI.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.143.suppl_1.P111
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 9
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    DNA methylation-based estimator of telomere length
    Impact Journals, LLC ; 2019
    In:  Aging Vol. 11, No. 16 ( 2019-08-18), p. 5895-5923
    Details
    In: Aging, Impact Journals, LLC, Vol. 11, No. 16 ( 2019-08-18), p. 5895-5923
    Type of Medium: Online Resource
    ISSN: 1945-4589
    URL: Issue
    URL: Article
    DOI: 10.18632/aging.v11i16
    DOI: 10.18632/aging.102173
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2535337-8
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  • 10
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    Long-term Impact of Temporal Sequence from Childhood Obesity to Hyperinsulinemia on Adult Metabolic Syndrome and Diabetes: The Bogalusa Heart Study
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-02-23)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-02-23)
    Abstract: This study aims to delineate the temporal relations between body mass index (BMI) and insulin in childhood and their impact on adult metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM).The longitudinal cohort consisted of 609 whites and 339 blacks who had BMI and fasting insulin measured twice in childhood (mean age = 10.5 years at baseline and 15.9 years at follow-up). Incident MetS and T2DM were identified in adulthood (mean age = 30.5 years). Cross-lagged panel and mediation analysis models were used. After adjusting for age, race, gender, and follow-up years, the cross-lagged path coefficient of BMI → insulin (β = 0.326, p  〈  0.001) was significantly greater than that of insulin → BMI (β = −0.023, p = 0.207) in childhood, with p  〈  0.001 for the difference in βs. The path coefficient for BMI → insulin was significantly greater in MetS than in non-MetS groups (0.510 vs 0.190, p  〈  0.001), and greater in hyperglycemia than in normoglycemia groups (0.503 vs 0.285, p = 0.026). The mediation effect of childhood insulin on the BMI-MetS and BMI-hyperglycemia associations was estimated at 19.2% (p  〈  0.001) and 18.3% (p  〈  0.001), respectively. These findings provide evidence that higher BMI levels precede hyperinsulinemia during childhood, and this one-directional relation plays a significant role in the development of MetS and T2DM in adult life.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/srep43422
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
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