scholarly journals Association of GrimAge DNA methylation components and 2-year mortality in the Health and Retirement Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 675-675
Author(s):  
Helen Meier ◽  
Colter Mitchell ◽  
Eileen Crimmins ◽  
Bharat Thyagarajan ◽  
Jessica Faul

Abstract DNA methylation (DNAm) patterns related to age and aging phenotypes (i.e., epigenetic clocks) are of growing interest as indicators of biological age and risk of negative health outcomes. We investigated associations between the components of GrimAge, an epigenetic clock estimated from DNAm patterns for seven blood protein levels and smoking pack years, and 2-year mortality in the Health and Retirement Study (HRS) to determine if any of the DNAm subcomponents were driving observed associations. A representative subsample of individuals who participated in the HRS 2016 Venus Blood Study were included in this analysis (N=3430). DNAm was measured with the Infinium Methylation EPIC BeadChip. Deaths that occurred between 2016 and 2018 contributed to 2-year mortality estimates (N=159, 4.5% of the sample). Weighted logistic regression estimated the association first between GrimAge and 2-year mortality and second between the DNAm subcomponents and 2-year mortality. All models were adjusted for age, sex, race/ethnicity, education, current smoking status, smoking pack years and cell composition of the biological sample. The average GrimAge for participants with and without 2-year mortality was 77 years 68 years respectively. A one-year increase in GrimAge was associated with 17% higher odds of 2-year mortality (95% CI: 1.16, 1.17). Two of the seven DNAm blood protein subcomponents of GrimAge (TIMP metallopeptidase inhibitor 1, adrenomedullin) and DNAm smoking pack years were associated with 2-year mortality and DNAm smoking pack years appeared to drive the overall GrimAge association with 2-year mortality. GrimAge was a better predictor of 2-year mortality than the DNAm subcomponents individually.

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Luhang Han ◽  
Hongmei Zhang ◽  
Akhilesh Kaushal ◽  
Faisal I. Rezwan ◽  
Latha Kadalayil ◽  
...  

Abstract Background Adolescence is a period characterized by major biological development, which may be associated with changes in DNA methylation (DNA-M). However, it is unknown to what extent DNA-M varies from pre- to post-adolescence, whether the pattern of changes is different between females and males, and how adolescence-related factors are associated with changes in DNA-M. Methods Genome-scale DNA-M at ages 10 and 18 years in whole blood of 325 subjects (n = 140 females) in the Isle of Wight (IOW) birth cohort was analyzed using Illumina Infinium arrays (450K and EPIC). Linear mixed models were used to examine DNA-M changes between pre- and post-adolescence and whether the changes were gender-specific. Adolescence-related factors and environmental exposure factors were assessed on their association with DNA-M changes. Replication of findings was attempted in the comparable Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Results In the IOW cohort, after controlling for technical variation and cell compositions at both pre- and post-adolescence, 15,532 cytosine–phosphate–guanine (CpG) sites (of 400,825 CpGs, 3.88%) showed statistically significant DNA-M changes from pre-adolescence to post-adolescence invariant to gender (false discovery rate (FDR) = 0.05). Of these 15,532 CpGs, 10,212 CpGs (66%) were replicated in the ALSPAC cohort. Pathway analysis using Ingenuity Pathway Analysis (IPA) identified significant biological pathways related to growth and development of the reproductive system, emphasizing the importance of this period of transition on epigenetic state of genes. In addition, in IOW, we identified 1179 CpGs with gender-specific DNA-M changes. In the IOW cohort, body mass index (BMI) at age 10 years, age of growth spurt, nonsteroidal drugs use, and current smoking status showed statistically significant associations with DNA-M changes at 15 CpGs on 14 genes such as the AHRR gene. For BMI at age 10 years, the association was gender-specific. Findings on current smoking status were replicated in the ALSPAC cohort. Conclusion Adolescent transition is associated with changes in DNA-M at more than 15K CpGs. Identified pathways emphasize the importance of this period of transition on epigenetic state of genes relevant to cell growth and immune system development.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S892-S893
Author(s):  
Fadi Youkhana ◽  
Yanyan Wu ◽  
Mika Thompson ◽  
Catherine M Pirkle

Abstract Type 2 diabetes (T2D) is a complex chronic disorder influenced by genetic and environmental factors. Studies that use a combined polygenetic score (PGS), calculated based on the number of risk alleles an individual may have, are rarely applied to a representative national sample. We used data from the Health and Retirement Study (HRS), a nationally representative study of older U.S. adults 50-years or older to examine the impact of PGS and behavioral risk factors (education, poverty ratio, BMI, smoking status, alcohol consumption and physical activity) with incident T2D. We used ethnic-straitifed Poisson generalized estimating equation (GEE) models with robust standard errors to estimate prevalence ratios (PRs) and risk ratios (RRs). Our sample included genotyped Black (N=2,823) and White (N=11,178) men and women.The highest PRs for T2D were among those in the 5th PGS quintile in both Whites (PR=2.24, 95%CI 1.89, 2.65, P-value <0.0001) and Blacks (PR=1.73, 95%CI 1.28,2.33, P-value 0.0003). The highest risk for T2D was among obese Whites (RR=3.35, 95%CI 2.93,3.82, P-value <0.0001) and Blacks (RR=1.60, 95%CI 1.28, 2.00, P-value <0.0001). Our findings found associations between PGS and T2D as well as some lifestyle factors among both Black and White individuals in a nationally representative sample with similar patterns in age, physical activity and poverty ratio. Our study supports the importance of including modifiable and non-modifiable life-style factors in the analysis of risk alleles for T2D to continue addressing the disparities between T2D risk between race/ethnicity groups


Author(s):  
Eileen M Crimmins ◽  
Bharat Thyagarajan ◽  
Morgan E Levine ◽  
David R Weir ◽  
Jessica Faul

Abstract Background Many DNA methylation-based indicators have been developed as summary measures of epigenetic aging. We examine the associations between 13 epigenetic clocks, including 4 second generation clocks, as well as the links of the clocks to social, demographic, and behavioral factors known to be related to health outcomes: sex, race/ethnicity, socioeconomic status, obesity, and lifetime smoking pack-years. Methods The Health and Retirement Study is the data source which is a nationally representative sample of Americans over age 50. Assessment of DNA methylation was based on the EPIC chip and epigenetic clocks were developed based on existing literature. Results The clocks vary in the strength of their relationships with age, with each other and with independent variables. Second generation clocks trained on health-related characteristics tend to relate more strongly to the sociodemographic and health behaviors known to be associated with health outcomes in this age group. Conclusions Users of this publicly available data set should be aware that epigenetic clocks vary in their relationships to age and to variables known to be related to the process of health change with age.


2021 ◽  
pp. 219256822110419
Author(s):  
Jose A Canseco ◽  
Michael Chang ◽  
Brian A Karamian ◽  
Jennifer Z Mao ◽  
Ariana A Reyes ◽  
...  

Study Design Retrospective case series. Objective To determine risk factors associated with prolonged opioid use after lumbar fusion and to elucidate the effect of opioid use on patient-reported outcome measures (PROMs) after surgery. Methods Patients who underwent 1–3 level lumbar decompression and fusion with at least one-year follow-up were identified. Opioid data were collected through the Pennsylvania Prescription Drug Monitoring Program. Preoperative “chronic use” was defined as consumption of >90 days in the one-year before surgery. Postoperative “prolonged use” was defined as a filled prescription 90-days after surgery. PROMs included the following: Short Form-12 Health Survey PCS-12 and MCS-12, ODI, and VAS-Back and Leg scores. Logistic regression was performed to determine independent predictors for prolonged opioid use. Results The final analysis included 260 patients. BMI >35 (OR: .44 [.20, .90], P = .03) and current smoking status (OR: 2.73 [1.14, 6.96], P = .03) significantly predicted postoperative opioid usage. Chronic opioid use before surgery was associated with greater improvements in MCS-12 (β= 5.26 [1.01, 9.56], P = .02). Patients with prolonged opioid use self-reported worse VAS-Back (3.4 vs 2.1, P = .003) and VAS-Leg (2.6 vs 1.2, P = .03) scores after surgery. Prolonged opioid use was associated with decreased improvement in VAS-Leg over time (β = .14 [.15, 1.85], P = .02). Conclusions Current smoking status and lower BMI were significantly predictive of prolonged opioid use. Excess opioid use before and after surgery significantly affected PROMs after lumbar fusion.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S683-S683
Author(s):  
Nicholas V Resciniti ◽  
Jaleel McNiel ◽  
Matthew Lohman

Abstract Research has shown there is currently an increasing prevalence of cognitive impairment and dementia in older adults. To date, there remains a paucity of research to explain this increase and research on early markers and risk factors are warranted. This study aims to assess the association of cognitively normal older adults who are frail and the development of cognitive impairment four years later. Data from the Health and Retirement Study – a nationally representative sample of older US adults – was used from 2004-2008 for individuals 65 and older (n=8,377). Frailty was categorized by using Fried’s phenotype model: individuals were grouped into frail, pre-frail, and robust. Cognitive impairment – a composite score that assessed memory recall and global mental status – was classified as scoring eight or less on a 35-point scale. After restricting to cognitively healthy individuals, logistic regression with weights was used to assess the association between frailty status and the development of cognitive impairment four years later. The model was adjusted for baseline age, gender, race, education years, smoking status, and chronic health issues (high blood pressure, diabetes, cancer, lung disease, heart disease, stroke, psychiatric problems, and arthritis). Frail individuals, compared to those who were robust, had increased odds of cognitive impairment (OR=1.74; 95% CI: 1.48-2.16), after fully adjusting. Evidence from this study suggest that frail individuals are more likely to become cognitively impaired over time. This provides a potential pathway of intervention to help delay or prevent the development of cognitive impairment in older US adults.


2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Roland J Thorpe ◽  
Ryon Cobb ◽  
Keyonna King ◽  
Marino A Bruce ◽  
Paul Archibald ◽  
...  

Abstract Background and Objectives Among the multiple factors posited to drive the health inequities that black men experience, the fundamental role of stress in the production of poor health is a key component. Allostatic load (AL) is considered to be a byproduct of stressors related to cumulative disadvantage. Exposure to chronic stress is associated with poorer mental health including depressive symptoms. Few studies have investigated how AL contributes to depressive symptoms among black men. The purpose of the cross-sectional study was to examine the association between AL and depressive symptoms among middle- to old age black men. Research Design and Methods This project used the 2010 and 2012 wave of the Health and Retirement Study enhanced face-to-face interview that included a biomarker assessment and psychosocial questionnaire. Depressive symptoms, assessed by the endorsement of 3 or more symptoms on the Center for Epidemiological Studies—Depression 8-item scale, was the outcome variable. The main independent variable, AL, score was calculated by summing the number values that were in the high range for that particular biomarker value scores ranging from 0 to 7. black men whose AL score was 3 or greater were considered to be in the high AL group. Modified Poisson regression was used to estimate prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs). Results There was a larger proportion of black men in the high AL group who reported depressive symptoms (30.0% vs. 20.0%) compared with black men in the low AL group. After adjusting for age, education, income, drinking, and smoking status, the prevalence of reporting 3 or more depressive symptoms was statistically significant among black men in the high AL group (PR = 1.61 [95% CI: 1.20–2.17]) than black men in the low AL group. Discussion and Implications Exposure to chronic stress is related to reporting 3 or more depressive symptoms among black men after controlling for potential confounders. Improving the social and economic conditions for which black men work, play, and pray is key to reducing stress, thereby potentially leading to the reporting of fewer depressive symptoms.


Author(s):  
Asiye Başusta ◽  
Murat Dağ

In this study, monthly changes of blood protein levels in rainbow trout were examined. For this purpose, fish samples were obtained from cages established on Keban Dam Lake (Elazığ). This study was carried out for one year and 10 fish with same age group were examined monthly. Firstly, total length and live weight of fish samples were measured and then blood samples were taken from caudal vein. Serum in blood samples were separated and total protein, albumin, globulin and fibrinogen levels in blood serum were determined. In the examined blood samples, the highest values were found as 4.52 g/dL for total protein, 2.37 g/dL for albumin, 2.15 g/dL for globulin in March and 198.74 mg/dL for fıbrinogen in January. On the other hand, the lowest values were obtained in the winter season for total protein, albumin and globulin, and in the summer season for fibrinogen. According to the statistical analysis, it was found that monthly changes of all determined values was significant. In addition, the changes of albumin, globulin and fibrinogen levels with the length and weight of fish were also found positive relationship. Monthly changes of all these values were statistically found significant.


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