The Health and Retirement Study (HRS) is a nationally representative longitudinal survey of more than 37 000 individuals over age 50 in 23 000 households in the USA. The survey, which has been ...fielded every 2 years since 1992, was established to provide a national resource for data on the changing health and economic circumstances associated with ageing at both individual and population levels. Its multidisciplinary approach is focused on four broad topics—income and wealth; health, cognition and use of healthcare services; work and retirement; and family connections. HRS data are also linked at the individual level to administrative records from Social Security and Medicare, Veteran’s Administration, the National Death Index and employer-provided pension plan information. Since 2006, data collection has expanded to include biomarkers and genetics as well as much greater depth in psychology and social context. This blend of economic, health and psychosocial information provides unprecedented potential to study increasingly complex questions about ageing and retirement. The HRS has been a leading force for rapid release of data while simultaneously protecting the confidentiality of respondents. Three categories of data—public, sensitive and restricted—can be accessed through procedures described on the HRS website (hrsonline.isr.umich.edu).
Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits ...within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using "second and third generation clocks," PhenoAge, GrimAge, and DunedinPACE, is consistently a significant predictor of health outcomes including cross-sectional cognitive dysfunction, functional limitations and chronic conditions assessed 2 y after DNAm measurement, and 4-y mortality. PC-based epigenetic age acceleration measures do not significantly change the relationship of DNAm-based age acceleration measures to health outcomes or mortality compared to earlier versions of these measures. While the usefulness of DNAm-based age acceleration as a predictor of later life health outcomes is quite clear, other factors such as demographics, SES, mental health, and health behaviors remain equally, if not more robust, predictors of later life outcomes.
Age-related changes in cognitive abilities are well-documented, and a very important indicator of health, functioning, and decline in later life. However, less is known about the course of cognitive ...functioning before and after retirement and specifically whether job characteristics during one's time of employment (i.e., higher vs. lower levels of mental work demands) moderate how cognition changes both before and after the transition to retirement. We used data from n = 4,182 (50% women) individuals in the Health and Retirement Study, a nationally representative panel study in the United States, across an 18 year time span (1992-2010). Data were linked to the O*NET occupation codes to gather information about mental job demands to examine whether job characteristics during one's time of employment moderates level and rate of change in cognitive functioning (episodic memory and mental status) both before and after retirement. Results indicated that working in an occupation characterized by higher levels of mental demands was associated with higher levels of cognitive functioning before retirement, and a slower rate of cognitive decline after retirement. We controlled for a number of important covariates, including socioeconomic (education and income), demographic, and health variables. Our discussion focuses on pathways through which job characteristics may be associated with the course of cognitive functioning in relation to the important transition of retirement. Implications for job design as well as retirement are offered.
Both social and genetic factors contribute to cognitive impairment and decline, yet genetic factors identified through genome-wide association studies (GWAS) explain only a small portion of trait ...variability. This “missing heritability” may be due to rare, potentially functional, genetic variants not assessed by GWAS, as well as gene-by-social factor interactions not explicitly modeled. Gene-by-social factor interactions may also operate differently across race/ethnic groups. We selected 39 genes that had significant, replicated associations with cognition, dementia, and related traits in published GWAS. Using gene-based analysis (SKAT/iSKAT), we tested whether common and/or rare variants were associated with episodic memory performance and decline either alone or through interaction with education in >10,000 European ancestry (EA) and >2200 African ancestry (AA) respondents from the Health and Retirement Study (HRS). Nine genes in EA and five genes in AA were associated with memory performance or decline (p < 0.05), and these effects did not attenuate after adjusting for education. Interaction between education and CLPTM1 on memory performance was significant in AA (p = 0.003; FDR-adjusted p = 0.038) and nominally significant in EA (p = 0.026). In both ethnicities, low memory performance was associated with CLPTM1 genotype (rs10416261) only for those with less than high school education, and effects persisted after adjusting for APOE ε4. For over 70% of gene-by-education interactions across the genome that were at least nominally significant in either ethnic group (p < 0.05), genetic effects were only observed for those with less than high school education. These results suggest that genetic effects on memory identified in this study are not mediated by education, but there may be important gene-by-education interactions across the genome, including in the broader APOE genomic region, which operate independently of APOE ε4. This work illustrates the importance of developing theoretical frameworks and methodological approaches for integrating social and genomic data to study cognition across ethnic groups.
•Investigates genetic effects on longitudinal trajectories of memory performance.•Evaluates whether education modifies genetic effects on memory trajectories.•Genetic effects on memory were not mediated by educational attainment.•Education may offset genetic influences on memory performance and decline.
Long-term psychosocial stress is strongly associated with negative physical and mental health outcomes, as well as adverse health behaviours; however, little is known about the role that stress plays ...on the epigenome. One proposed mechanism by which stress affects DNA methylation is through health behaviours. We conducted an epigenome-wide association study (EWAS) of cumulative psychosocial stress (
= 2,689) from the Health and Retirement Study (mean age = 70.4 years), assessing DNA methylation (Illumina Infinium HumanMethylationEPIC Beadchip) at 789,656 CpG sites. For identified CpG sites, we conducted a formal mediation analysis to examine whether smoking, alcohol use, physical activity, and body mass index (BMI) mediate the relationship between stress and DNA methylation. Nine CpG sites were associated with psychosocial stress (all
< 9E-07; FDR q < 0.10). Additionally, health behaviours and/or BMI mediated 9.4% to 21.8% of the relationship between stress and methylation at eight of the nine CpGs. Several of the identified CpGs were in or near genes associated with cardiometabolic traits, psychosocial disorders, inflammation, and smoking. These findings support our hypothesis that psychosocial stress is associated with DNA methylation across the epigenome. Furthermore, specific health behaviours mediate only a modest percentage of this relationship, providing evidence that other mechanisms may link stress and DNA methylation.
Abstract
Objectives
This study aims to examine the relationship between childhood socioeconomic position (SEP) and cognitive function in later life within nationally representative samples of older ...adults in the United States and England, investigate whether these effects are mediated by later-life SEP, and determine whether social mobility from childhood to adulthood affects cognitive function and decline.
Method
Using data from the Health and Retirement Study (HRS) and the English Longitudinal Survey of Ageing (ELSA), we examined the relationships between measures of SEP, cognitive performance and decline using individual growth curve models.
Results
High childhood SEP was associated with higher cognitive performance at baseline in both cohorts and did not affect the rate of decline. This benefit dissipated after adjusting for education and adult wealth in the United States. Respondents with low childhood SEP, above median education, and high adult SEP had better cognitive performance at baseline than respondents with a similar childhood background and less upward mobility in both countries.
Discussion
These findings emphasize the impact of childhood SEP on cognitive trajectories among older adults. Upward mobility may partially compensate for disadvantage early in life but does not protect against cognitive decline.
Background
There is a large body of evidence linking muscular weakness, as determined by low grip strength, to a host of negative ageing‐related health outcomes. Given these links, grip strength has ...been labelled a ‘biomarker of aging’; and yet, the pathways connecting grip strength to negative health consequences are unclear. The objective of this study was to determine whether grip strength was associated with measures of DNA methylation (DNAm) age acceleration.
Methods
Middle age and older adults from the 2006 to 2008 waves of the Health and Retirement Study with 8–10 years of follow‐up were included. Cross‐sectional and longitudinal regression modelling was performed to examine the association between normalized grip strength (NGS) and three measures of DNAm age acceleration, adjusting for cell composition, sociodemographic variables and smoking. Longitudinal modelling was also completed to examine the association between change in absolute grip strength and DNAm age acceleration. The three DNAm clocks used for estimating age acceleration include the established DunedinPoAm, PhenoAge and GrimAge clocks.
Results
There was a robust and independent cross‐sectional association between NGS and DNAm age acceleration for men using the DunedinPoAm (β: −0.36; P < 0.001), PhenoAge (β: −8.27; P = 0.01) and GrimAge (β: −4.56; P = 0.01) clocks and for women using the DunedinPoAm (β: −0.36; P < 0.001) and GrimAge (β: −4.46; P = 0.01) clocks. There was also an independent longitudinal association between baseline NGS and DNAm age acceleration for men (β: −0.26; P < 0.001) and women (β: −0.36; P < 0.001) using the DunedinPoAm clock and for women only using the PhenoAge (β: −8.20; P < 0.001) and GrimAge (β: −5.91; P < 0.001) clocks. Longitudinal modelling revealed a robust association between change in grip strength from wave 1 to wave 3 was independently associated with PhenoAgeAA (β: −0.13; 95% CI: −0.23, −0.03) and GrimAgeAA (β: −0.07; 95% CI: −0.14, −0.01) in men only (both P < 0.05).
Conclusions
Our findings provide some initial evidence of age acceleration among men and women with lower NGS and loss of strength over time. Future research is needed to understand the extent to which DNAm age mediates the association between grip strength and chronic disease, disability and mortality.
Later life cognitive function is influenced by genetics as well as early- and later-life socioeconomic context. However, few studies have examined the interaction between genetics and early childhood ...factors. Using gene-based tests (iSKAT/iSKAT-O), we examined whether common and/or rare exonic variants in 39 gene regions previously associated with cognitive performance, dementia, and related traits had an interaction with childhood socioeconomic context (parental education and financial strain) on memory performance or decline in European ancestry (EA, N=10,468) and African ancestry (AA, N=2,252) participants from the Health and Retirement Study. Of the 39 genes, 22 in EA and 19 in AA had nominally significant interactions with at least one childhood socioeconomic measure on memory performance and/or decline; however, all but one (father's education by SLC24A4 in AA) were not significant after multiple testing correction (FDR <0.05). In trans-ethnic meta-analysis, two genes interacted with childhood socioeconomic context (FDR <0.05): mother's education by MS4A4A on memory performance, and father's education by SLC24A4 on memory decline. Both interactions remained significant (p<0.05) after adjusting for respondent's own educational attainment, APOE ε4 status, lifestyle factors, BMI, and comorbidities. For both interactions in EA and AA, the genetic effect was stronger in participants with low parental education. Examination of common and rare variants in genes discovered through GWAS shows that childhood context may interact with key gene regions to jointly impact later life memory function and decline. Genetic effects may be more salient for those with lower childhood socioeconomic status.
Polygenic scores are a strategy to aggregate the small, additive effects of single nucleotide polymorphisms across the genome. With phenotypes like Alzheimer's disease, which have a strong and ...well-established genomic locus (APOE), the cumulative effect of genetic variants outside of this area has not been well established in a population-representative sample.
Here we examine the association between polygenic scores for Alzheimer's disease both with and without the APOE region (chr19: 45,384,477 to 45,432,606, build 37/hg 19) at different P value thresholds and dementia. We also investigate the addition of APOE-ε4 carrier status and its effect on the polygenic score-dementia association in the Health and Retirement Study using generalized linear models accounting for repeated measures by individual and use a binomial distribution, logit link, and unstructured correlation structure.
In a large sample of European ancestry participants of the Health and Retirement Study (n = 9872) with an average of 5.2 (standard deviation 1.8) visit spaced two years apart, we found that including the APOE region through weighted variants in a polygenic score was insufficient to capture the large amount of risk attributed to this region. We also found that a polygenic score with a P value threshold of 0.01 had the strongest association with the odds of dementia in this sample (odds ratio = 1.10 95%CI 1.0 to 1.2).
We recommend removing the APOE region from polygenic score calculation and treating the APOE locus as an independent covariate when modeling dementia. We also recommend using a moderately conservative P value threshold (e.g. 0.01) when creating polygenic scores for Alzheimer's disease on dementia. These recommendations may help elucidate relationships between polygenic scores and regions of strong significance for phenotypes similar to Alzheimer's disease.
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