TY - JOUR T1 - Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up. JF - Alzheimer Dis Assoc Disord Y1 - 2016 A1 - Jessica R Marden A1 - Elizabeth R Mayeda A1 - Stefan Walter A1 - Vivot, Alexandre A1 - Tchetgen Tchetgen, Eric J A1 - Ichiro Kawachi A1 - M. Maria Glymour KW - Alzheimer disease KW - Black or African American KW - ethnicity KW - Female KW - Follow-Up Studies KW - Genome-Wide Association Study KW - Humans KW - Male KW - Memory Disorders KW - Middle Aged KW - Risk Factors KW - United States KW - White People AB -

Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores measured 1 to 8 times between 1998 and 2012 (average baseline age=62), we calculated weighted polygenic risk scores [AD Genetic Risk Score (AD-GRS)] using the top 22 AD-associated loci, and an alternative score excluding apolipoprotein E (APOE) (AD-GRSexAPOE). We used generalized linear models with AD-GRS-by-age and AD-GRS-by-age interactions (age centered at 70) to predict memory decline. Average NHB decline was 26% faster than NHW decline (P<0.001). Among NHW, 10% higher AD-GRS predicted faster memory decline (linear β=-0.058 unit decrease over 10 y; 95% confidence interval,-0.074 to -0.043). AD-GRSexAPOE also predicted faster decline for NHW, although less strongly. Among NHB, AD-GRS predicted faster memory decline (linear β=-0.050; 95% confidence interval, -0.106 to 0.006), but AD-GRSexAPOE did not. Our nonsignificant estimate among NHB may reflect insufficient statistical power or a misspecified AD-GRS among NHB as an overwhelming majority of genome-wide association studies are conducted in NHW. A polygenic score based on previously identified AD loci predicts memory loss in US blacks and whites.

VL - 30 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26756387?dopt=Abstract U4 - Gene Ontology/Diseases/Genes/Proteins ER - TY - JOUR T1 - Use of life course work-family profiles to predict mortality risk among US women JF - American journal of public health Y1 - 2015 A1 - Erika L. Sabbath A1 - Guevara, Ivan Mejia A1 - M. Maria Glymour A1 - Lisa F Berkman KW - Adult children KW - Event History/Life Cycle KW - Health Conditions and Status KW - Other KW - Women and Minorities AB - OBJECTIVES: We examined relationships between US women's exposure to midlife work-family demands and subsequent mortality risk. METHODS: We used data from women born 1935 to 1956 in the Health and Retirement Study to calculate employment, marital, and parenthood statuses for each age between 16 and 50 years. We used sequence analysis to identify 7 prototypical work-family trajectories. We calculated age-standardized mortality rates and hazard ratios (HRs) for mortality associated with work-family sequences, with adjustment for covariates and potentially explanatory later-life factors. RESULTS: Married women staying home with children briefly before reentering the workforce had the lowest mortality rates. In comparison, after adjustment for age, race/ethnicity, and education, HRs for mortality were 2.14 (95 confidence interval CI =1.58, 2.90) among single nonworking mothers, 1.48 (95 CI=1.06, 1.98) among single working mothers, and 1.36 (95 CI=1.02, 1.80) among married nonworking mothers. Adjustment for later-life behavioral and economic factors partially attenuated risks. CONCLUSIONS: Sequence analysis is a promising exposure assessment tool for life course research. This method permitted identification of certain lifetime work-family profiles associated with mortality risk before age 75 years. PB - 105 VL - 105 IS - 4 N1 - Times Cited: 0 0 U4 - mortality risk/mortality risk/WOMEN/midlife/work-family balance/life Course ER - TY - JOUR T1 - Using marginal structural models to estimate the direct effect of adverse childhood social conditions on onset of heart disease, diabetes, and stroke. JF - Epidemiology Y1 - 2012 A1 - Nandi, Arijit A1 - M. Maria Glymour A1 - Ichiro Kawachi A1 - Tyler J VanderWeele KW - Age Factors KW - Age of Onset KW - Child KW - Diabetes Mellitus KW - Educational Status KW - Female KW - Heart Diseases KW - Humans KW - Income KW - Linear Models KW - Male KW - Middle Aged KW - Models, Statistical KW - Risk Factors KW - Social Class KW - Social Conditions KW - Socioeconomic factors KW - Stroke KW - United States AB -

BACKGROUND: Early-life socioeconomic status (SES) is associated with adult chronic disease, but it is unclear whether this effect is mediated entirely via adult SES or whether there is a direct effect of adverse early-life SES on adult disease. Major challenges in evaluating these alternatives include imprecise measurement of early-life SES and bias in conventional regression methods to assess mediation. In particular, conventional regression approaches to direct effect estimation are biased when there is time-varying confounding of the association between adult SES and chronic disease by chronic disease risk factors.

METHODS: First-reported heart disease, diabetes, and stroke diagnoses were assessed in a national sample of 9760 Health and Retirement Study participants followed biennially from 1992 through 2006. Early-life and adult SES measures were derived using exploratory and confirmatory factor analysis. Early-life SES was measured by parental education, father's occupation, region of birth, and childhood rural residence. Adult SES was measured by respondent's education, occupation, labor force status, household income, and household wealth. Using marginal structural models, we estimated the direct effect of early-life SES on chronic disease onset that was not mediated by adult SES. Marginal structural models were estimated with stabilized inverse probability-weighted log-linear models to adjust for risk factors that may have confounded associations between adult SES and chronic disease.

RESULTS: During follow-up, 24%, 18%, and 9% of participants experienced first onset of heart disease, diabetes, and stroke, respectively. Comparing those in the most disadvantaged with the least disadvantaged quartile, early-life SES was associated with coronary heart disease (risk ratio = 1.30 [95% confidence interval = 1.12-1.51]) and diabetes (1.23 [1.02-1.48]) and marginally associated with stroke via pathways not mediated by adult SES.

CONCLUSIONS: Our results suggest that early-life socioeconomic experiences directly influence adult chronic disease outcomes.

PB - 23 VL - 23 IS - 2 N1 - Nandi, Arijit Glymour, M Maria Kawachi, Ichiro VanderWeele, Tyler J HD060696/HD/NICHD NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Epidemiology. 2012 Mar;23(2):223-32. U1 - http://www.ncbi.nlm.nih.gov/pubmed/22317806?dopt=Abstract U2 - PMC3414366 U4 - Age Factors/Age of Onset/Child/Diabetes Mellitus/Educational Status/Female/Heart Diseases/Income/Linear Models/Linear Models/Models, Statistical/Risk Factors/Social Class/Social Conditions/Socioeconomic Factors/Stroke ER -