Dataset Information

Mortality and Obesity Among U.S. Older Adults: The Role of Polygenic Risk.

ABSTRACT:

Objectives

To examine the relationship between obesity and mortality as a function of polygenic risk for obesity among older U.S. adults.

Method

Using data from the 1994-2014 Health and Retirement Study in conjunction with genome-wide data, we evaluated the risk of mortality as a function of obesity classification, an individual's polygenic risk score (PGS) for obesity, and their interaction, stratified by sex. We conducted our analyses using cox proportional hazard models.

Results

Among those with an average PGS for obesity (8,143 [68.8%]), obese I (hazard ratio [HR] = 0.79, p = .336) adults show no difference in their risk for mortality and obese II/III (HR = 3.17, p = .000) adults present higher risk of mortality relative to non-obese adults. The interaction of obesity classification and PGS suggests that obese II/III respondents with low PGS in the total sample (HR = 2.71, p = .006) and among women (HR = 3.02, p = .023) are at significantly higher risk of death when compared to obese II/III respondents with average or high PGS.

Discussion

We posit that these findings suggest that the pathway to obesity, in this case, more socio-behavioral rather than genetic, may influence subsequent risk of death in older adults. We suggest that practitioners and population researchers be mindful of these pathways as to better identify and understand mortality risk.

SUBMITTER: Vinneau JM

PROVIDER: S-EPMC7813195 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Mortality and Obesity Among U.S. Older Adults: The Role of Polygenic Risk.

Vinneau Justin M JM Huibregtse Brooke M BM Laidley Thomas M TM Goode Joshua A JA Boardman Jason D JD

The journals of gerontology. Series B, Psychological sciences and social sciences 20210101 2

<h4>Objectives</h4>To examine the relationship between obesity and mortality as a function of polygenic risk for obesity among older U.S. adults.<h4>Method</h4>Using data from the 1994-2014 Health and Retirement Study in conjunction with genome-wide data, we evaluated the risk of mortality as a function of obesity classification, an individual's polygenic risk score (PGS) for obesity, and their interaction, stratified by sex. We conducted our analyses using cox proportional hazard models.<h4>Res ...[more]

PMID: 31805181

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Project description:Dementia incidence increases steadily with age at rates that may vary across racial groups. This racial disparity may be attributable to polygenic risk, as well as lifestyle and behavioural factors. We examined whether Alzheimer's disease polygenic score and race predict Alzheimer's disease and other related dementia incidence differentially by sex and mediation through polygenic scores for other health and behavioural conditions. We used longitudinal data from the nationally representative Health and Retirement Study. We restricted participants to those with complete data on 31 polygenic scores, including Alzheimer's disease polygenic score (2006-2012). Among participants aged 55 years and older in 2008, we excluded those with any memory problems between 2006 and 2008 and included those with complete follow-up on incident Alzheimer's disease and all-cause dementia, between 2010 and 2018 (N = 9683), based on self- or proxy-diagnosis every 2 years (2010, 2012, 2014, 2016 and 2018). Cox proportional hazards and 4-way decomposition models were conducted. Analyses were also stratified by sex and by race. There were racial differences in all-cause dementia incidence (age and sex-adjusted model, per standard deviation: hazard ratio, HR = 1.34, 95% confidence interval, CI: 1.09-1.65, P = 0.007), partially driven by educational attainment and income. We also found independent associations of race (age and sex-adjusted model, African American versus White adults: HR = 2.07, 95% CI: 1.52-2.83, P < 0.001) and Alzheimer's disease polygenic score (age and sex-adjusted model, per SD: HR = 1.37, 95% CI: 1.00-1.87, P < 0.001) with Alzheimer's disease incidence, including sex differences whereby women had a stronger effect of Alzheimer's disease polygenic score on Alzheimer's disease incidence compared with men (P < 0.05 for sex by Alzheimer's disease polygenic score interaction) adjusting for race and other covariates. The total impact of Alzheimer's disease polygenic scores on Alzheimer's disease incidence was mostly direct, while the effect of race on all-cause dementia incidence was mediated through socio-economic, lifestyle and health-related factors. Finally, among the 30 polygenic scores we examined, the total effects on the pathway Alzheimer's disease polygenic score --> Other polygenic score --> Incident Alzheimer's or all-cause dementia, were statistically significant for all, driven primarily by the controlled direct effect (P< 0. 001). In conclusion, both race and Alzheimer's disease polygenic scores were associated independently with Alzheimer's disease and all-cause dementia incidence. Alzheimer's disease polygenic score was more strongly linked to incident Alzheimer's disease among women, while racial difference in all-cause dementia was explained by other factors including socio-economic status.

Dataset Information

Mortality and Obesity Among U.S. Older Adults: The Role of Polygenic Risk.

Objectives

Method

Results

Discussion

Publications

Mortality and Obesity Among U.S. Older Adults: The Role of Polygenic Risk.

Similar Datasets

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