scholarly journals Polygenic scores for education, health, and personality as predictors of subjective age among older individuals of European ancestry: Evidence from the Health and Retirement Study.

2019 ◽  
Vol 34 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Yannick Stephan ◽  
Angelina R. Sutin ◽  
Anna Kornadt ◽  
Antonio Terracciano
Keyword(s):  
European Ancestry ◽  
Health And Retirement Study ◽  
Older Individuals ◽  
Subjective Age ◽  
Polygenic Scores ◽  
Retirement Study

scholarly journals Considering the APOE locus in Alzheimer’s disease polygenic scores in the Health and Retirement Study: a longitudinal panel study

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Erin B. Ware ◽  
Jessica D. Faul ◽  
Colter M. Mitchell ◽  
Kelly M. Bakulski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Repeated Measures ◽  
Panel Study ◽  
European Ancestry ◽  
Health And Retirement Study ◽  
Carrier Status ◽  
Polygenic Score ◽  
Polygenic Scores ◽  
Retirement Study

Abstract Background 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. Methods 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. Results 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). Conclusion 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.

Major Discrimination Experiences, Education, and Genes

2019 ◽  
Vol 32 (7-8) ◽  
pp. 753-763
Author(s):  
Aniruddha Das
Keyword(s):  
Educational Attainment ◽  
Life Course ◽  
Mediation Analysis ◽  
Healthy Aging ◽  
Genetic Influences ◽  
Health And Retirement Study ◽  
Direct Effects ◽  
Polygenic Scores ◽  
Retirement Study

Objectives: Rather than acting as a buffer, educational attainment has a known positive linkage with major experiences of lifetime discrimination. Recently established genetic roots of education, then, may also influence such reports. The current study examined these patterns. Methods: Data were from the 2010 wave of the Health and Retirement Study. Polygenic scores indexed one’s genetic propensity for more education. Mediation analysis was through counterfactual methods. Results: Among Whites as well as Blacks, genetic antecedents of education also elevated discrimination reports. Part of this influence was channeled through education. At least among Whites, direct effects were also found. Discussion: Major discrimination experiences seem partly rooted in genes. Mechanisms are tentatively suggested. Direct genetic influences, in particular, indicate potential confounding of previously estimated linkages between discrimination and health or life course factors. Given the range of these prior results, and their implications for healthy aging, investigation of these possibilities is needed.

scholarly journals Genetic heterogeneity in depressive symptoms following the death of a spouse: Polygenic score analysis of the US Health and Retirement Study

2016 ◽  
Author(s):  
Benjamin W. Domingue ◽  
Hexuan Liu ◽  
Aysu Okbay ◽  
Daniel W. Belsky
Keyword(s):  
Older Adults ◽  
Depressive Symptoms ◽  
Life Stress ◽  
Genome Wide Association Study ◽  
The United States ◽  
Health And Retirement Study ◽  
Polygenic Score ◽  
Polygenic Scores ◽  
Retirement Study

AbstractExperience of stressful life events is associated with risk of depression. Yet many exposed individuals do not become depressed. A controversial hypothesis is that genetic factors influence vulnerability to depression following stress. This hypothesis is most commonly tested with a “diathesis-stress” model, in which genes confer excess vulnerability. We tested an alternative model, in which genes may buffer against the depressogenic effects of life stress. We measured the hypothesized genetic buffer using a polygenic score derived from a published genome-wide association study (GWAS) of subjective wellbeing. We tested if married older adults who had higher polygenic scores were less vulnerable to depressive symptoms following the death of their spouse as compared to age-peers who had also lost their spouse and who had lower polygenic scores. We analyzed data from N=9,453 non-Hispanic white adults in the Health and Retirement Study (HRS), a population-representative longitudinal study of older adults in the United States. HRS adults with higher wellbeing polygenic scores experienced fewer depressive symptoms during follow-up. Those who survived death of their spouses during follow-up (n=1,829) experienced a sharp increase in depressive symptoms following the death and returned toward baseline over the following two years. Having a higher polygenic score buffered against increased depressive symptoms following a spouse's death. Effects were small and clinical relevance is uncertain, although polygenic score analyses may provide clues to behavioral pathways that can serve as therapeutic targets. Future studies of gene-environment interplay in depression may benefit from focus on genetics discovered for putative protective factors.

The Changing Face of Debt and Financial Fragility at Older Ages

2018 ◽  
Vol 108 ◽  
pp. 407-411 ◽  
Author(s):  
Annamaria Lusardi ◽  
Olivia S. Mitchell ◽  
Noemi Oggero
Keyword(s):  
Policy Implications ◽  
Financial Fragility ◽  
Health And Retirement Study ◽  
Older Individuals ◽  
Older Americans ◽  
Down Payments ◽  
Using Data ◽  
Retirement Study

We investigate changes in older individuals' financial fragility as they stand on the verge of retirement. Using data from the Health and Retirement Study (HRS), we compare how debt has changed for successive cohorts of people age 56–61. Our analysis shows that recent older Americans close to retirement hold more debt, and hence face greater financial insecurity, than earlier generations. This is primarily due to having bought more expensive homes with smaller down payments. We discuss possible policy implications.

scholarly journals How Does Subjective Age Get “Under the Skin”? The Association Between Biomarkers and Feeling Older or Younger Than One’s Age: The Health and Retirement Study

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Bharat Thyagarajan ◽  
Nathan Shippee ◽  
Helen Parsons ◽  
Sithara Vivek ◽  
Eileen Crimmins ◽  
...  
Keyword(s):  
Reference Group ◽  
Inflammatory Marker ◽  
Endocrine Function ◽  
Stress Index ◽  
Chronological Age ◽  
Health And Retirement Study ◽  
Subjective Age ◽  
Reference Category ◽  
Age Related ◽  
Retirement Study

Abstract Background and Objectives Though subjective age is a well-recognized risk factor for several chronic diseases, the biological basis for these associations remains poorly understood. Research Design and Methods We used new comprehensive biomarker data from the 2016 wave of the nationally representative Health and Retirement Study (HRS) to evaluate the association between biomarker levels and self-reported subjective age in a subset of 3,740 HRS participants who provided a blood sample. We measured biomarkers in seven biological domains associated with aging: inflammation, glycemia, lipids, liver function, endocrine function, renal function, and cardiac function. The primary outcome was the age discrepancy score (subjective age − chronological age) categorized as those who felt younger, older, or the same as their chronological age (reference group). Analyses adjusted for comprehensive psychosocial factors (chronic stress index, depression score), demographic factors (race, sex, body mass index, marital status, physical activity), and prevalence of chronic health conditions (comorbidity index). Results The prevalence of clinically relevant reduced levels of albumin concentrations was lower in those who felt younger (8.8% vs. 16.0%; p = .006) and higher in those who felt older (20.4% vs. 16.0%; p = .03) when compared with the reference category. The prevalence of clinically significant elevation in liver enzymes such as alanine aminotransferase was also significantly lower among those who felt younger (7.1% vs. 8.6%; p = .04) when compared with the reference category. Prevalence of clinically elevated levels in cystatin C was also lower among those who felt younger when compared with the reference category (50.0% vs. 59.1%; p = .04). There was no association between lipids, glucose, or C-reactive protein (inflammatory marker) and subjective age categories. Discussion and Implications These results suggest that people who feel younger may have favorable biomarker profiles and as a result may have lower prevalence of age-related diseases when compared with those who feel older or those who feel the same as their chronological age.

scholarly journals Genetic basis of motoric cognitive risk syndrome in the Health and Retirement Study

Neurology ◽  
2019 ◽  
Vol 92 (13) ◽  
pp. e1427-e1434 ◽  
Author(s):  
Sanish Sathyan ◽  
Tao Wang ◽  
Emmeline Ayers ◽  
Joe Verghese
Keyword(s):  
Waist Circumference ◽  
Well Being ◽  
European Ancestry ◽  
Weighted Sums ◽  
Health And Retirement Study ◽  
Cognitive Complaints ◽  
Genetic Traits ◽  
Cognitive Risk ◽  
Retirement Study ◽  
Subjective Cognitive Complaints

ObjectiveTo examine polygenic inheritance of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of subjective cognitive complaints and slow gait.MethodsWe analyzed 4,915 individuals, age 65 years and above, with European ancestry (mean age 75.0 ± 6.8 years, 56.6% women) in the Health and Retirement Study. Polygenic scores (PGS) were calculated as weighted sums of the effect of single nucleotide polymorphisms, with effect sizes derived from genome-wide association studies. The association between PGSs of 9 phenotypes (general cognition, body mass index [BMI], mean arterial pressure, education, Alzheimer disease [AD], neuroticism, well-being, waist circumference, and depressive symptoms) and MCR as well as its key components (cognitive complaints and slow gait) were examined by logistic regression, adjusting for age, sex, education, and genetic ancestry, and reported as odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThere were 260 prevalent MCR cases, 529 with slow gait, and 1,928 with subjective cognitive complaints. Higher PGSs for BMI (OR 1.22, 95% CI 1.07–1.39) and waist circumference (OR 1.23, 95% CI 1.07–1.40) were associated with MCR, and PGS of AD showed a suggestive association (OR 1.16, 95% CI 1.02–1.32). Higher PGS for neuroticism (OR 1.10, 95% CI 1.03–1.18) was associated with cognitive complaints, whereas higher well-being PGS (OR 0.92, 95% CI 0.87–0.98) was protective. PGS for BMI (OR 1.16, 95% CI 1.06–1.28), waist circumference (OR 1.19, 95% CI 1.08–1.31), and AD (OR 1.13, 95% CI 1.03–1.24) was associated with slow gait.ConclusionObesity-related genetic traits increase risk of MCR syndrome; further investigation is required to identify potential therapeutic targets.

scholarly journals Genetic evidence for natural selection in humans in the contemporary United States

2016 ◽  
Author(s):  
Jonathan Beauchamp
Keyword(s):  
Natural Selection ◽  
European Ancestry ◽  
Age At Menarche ◽  
The Past ◽  
Representative Study ◽  
Polygenic Scores ◽  
The Us ◽  
Contemporary United States ◽  
Retirement Study ◽  
Selection Of

AbstractRecent findings from molecular genetics now make it possible to test directly for natural selection by analyzing whether genetic variants associated with various phenotypes have been under selection. I leverage these findings to construct polygenic scores that use individuals’ genotypes to predict their body mass index, educational attainment (EA), glucose concentration, height, schizophrenia, total cholesterol, and (in females) age at menarche. I then examine associations between these scores and fitness to test whether natural selection has been occurring. My study sample includes individuals of European ancestry born between 1931 and 1953 in the Health and Retirement Study, a representative study of the US population. My results imply that natural selection has been slowly favoring lower EA in both females and males, and are suggestive that natural selection may have favored a higher age at menarche in females. For EA, my estimates imply a rate of selection of about -1.5 months of education per generation (which pales in comparison with the increases in EA observed in contemporary times). Though they cannot be projected over more than one generation, my results provide additional evidence that humans are still evolving—albeit slowly, especially when compared to the rapid secular changes that have occurred over the past few generations due to cultural and environmental factors.

scholarly journals Genetic evidence for natural selection in humans in the contemporary United States

2016 ◽  
Vol 113 (28) ◽  
pp. 7774-7779 ◽  
Author(s):  
Jonathan P. Beauchamp
Keyword(s):  
Natural Selection ◽  
European Ancestry ◽  
Age At Menarche ◽  
Representative Study ◽  
Polygenic Scores ◽  
The Us ◽  
Rapid Changes ◽  
Contemporary United States ◽  
Retirement Study ◽  
Selection Of

Recent findings from molecular genetics now make it possible to test directly for natural selection by analyzing whether genetic variants associated with various phenotypes have been under selection. I leverage these findings to construct polygenic scores that use individuals’ genotypes to predict their body mass index, educational attainment (EA), glucose concentration, height, schizophrenia, total cholesterol, and (in females) age at menarche. I then examine associations between these scores and fitness to test whether natural selection has been occurring. My study sample includes individuals of European ancestry born between 1931 and 1953 who participated in the Health and Retirement Study, a representative study of the US population. My results imply that natural selection has been slowly favoring lower EA in both females and males, and are suggestive that natural selection may have favored a higher age at menarche in females. For EA, my estimates imply a rate of selection of about −1.5 mo of education per generation (which pales in comparison with the increases in EA observed in contemporary times). Although they cannot be projected over more than one generation, my results provide additional evidence that humans are still evolving—albeit slowly, especially compared with the rapid changes that have occurred over the past few generations due to cultural and environmental factors.

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