TY - JOUR T1 - Longitudinal Examination of an Ethnic Paradox of Stress and Mental Health in Older Black and Latinx Adults. JF - Clinical Gerontologist Y1 - 2023 A1 - Thalida E. Arpawong A1 - Sakuma, Kari-Lyn K A1 - Espinoza, Lilia A1 - Huh, Jimi KW - Depressive symptoms KW - Health Disparities KW - physical functioning KW - psychological resilience KW - Race/ethnicity KW - Stressful Life Events AB -

OBJECTIVES: To explain the ethnic paradox of mental health in aging, we evaluated whether Black and Latinx older adults experience (1) fewer depressive symptoms (DepSx), but more physical problems, and (2) greater psychological resilience as a result of life stressors than White older adults.

METHODS: DepSx, physical health, and recent stress were obtained biennially from 25,893 older adults (77% White, 15% Black, 9% Latinx) in the U.S. Health and Retirement Study, across 16 years. Psychological resilience, lifetime stress, and discrimination experiences were available for 13,655 individuals. We conducted mixed-effects and linear regression analyses.

RESULTS: For Blacks and Latinxs, experiencing more-than-usual stress events was associated with less increase in DepSx compared to Whites, although on average Blacks and Latinxs experience more DepSx. Black adults showed worse physical health than White adults and weaker effects of stress on psychological resilience despite experiencing more stress of all types. Findings were mixed for Latinxs.

CONCLUSIONS: Studying effects of time-varying stress on changes in health and multiple stressors on psychological resilience by race/ethnicity elucidates mechanisms for later-age health disparities.

CLINICAL IMPLICATIONS: Cross-sectional evaluations of stress and psychological health in a clinical setting may provide incomplete appraisals of health risks for Black and Latinx older Americans.

VL - 46 IS - 1 ER - TY - JOUR T1 - Genetic variation in ALDH4A1 predicts muscle health over the lifespan and across species JF - Elife Y1 - 2022 A1 - Villa, Osvaldo A1 - Stuhr, Nicole L. A1 - Yen, Chia-An A1 - Eileen M. Crimmins A1 - Thalida E. Arpawong A1 - Curran, Sean P. KW - Genetic Variation KW - muscle health AB - Environmental stress can negatively impact organismal aging, however, the long-term impact of endogenously derived reactive oxygen species from normal cellular metabolism remains less clear. Here we define the evolutionarily conserved mitochondrial enzyme ALH-6/ALDH4A1 as a biomarker for age-related changes in muscle health by combining C. elegans genetics and a gene-wide association study (GeneWAS) from aged human participants of the US Health and Retirement Study (HRS)1–4. In a screen for mutations that activate SKN-1-dependent oxidative stress responses in the muscle of C. elegans5–7, we identified 96 independent genetic mutants harboring loss-of-function alleles of alh-6, exclusively. These genetic mutations map across the ALH-6 polypeptide, which lead to age-dependent loss of muscle health. Intriguingly, genetic variants in ALDH4A1 differentially impact age-related muscle function in humans. Taken together, our work uncovers mitochondrial alh-6/ALDH4A1 as a critical component of normal muscle aging across species and a predictive biomarker for muscle health over the lifespan.Competing Interest StatementThe authors have declared no competing interest. VL - 11 IS - e74308 ER - TY - JOUR T1 - A longitudinal study shows stress proliferation effects from early childhood adversity and recent stress on risk for depressive symptoms among older adults. JF - Aging & Mental Health Y1 - 2022 A1 - Thalida E. Arpawong A1 - Mekli, Krisztina A1 - Lee, Jinkook A1 - Drystan F. Phillips A1 - Margaret Gatz A1 - Carol A Prescott KW - adverse child events KW - depression KW - Mental Health KW - stress generation KW - Trauma AB -

We evaluated whether the effects of recent stressful life events (SLEs) and early childhood adversities (ECAs) on depressive symptoms are consistent between men and women and across older age, and whether there was evidence for the following: stress sensitization, whereby the psychological impact of SLEs is greater for individuals with ECAs compared with those without; or stress proliferation effect, whereby those with ECAs are more likely to report more SLEs than those without ECAs to effect depressive symptoms. ECAs, SLEs in the past two years, and current depressive symptoms through a modified CES-D were obtained from 11,873 individuals participating in a population representative study of older adults, yielding 82,764 observations. Mixed-effects regression models on depressive symptoms were constructed to control for multiple observations per participant and evaluate within-person effects over time, thereby reducing bias from reverse causation. Results suggest a stress proliferation effect and do not support stress sensitization. ECAs contribute to vulnerability for depressive symptoms, with a dosage effect for each additional ECA. Recent SLEs result in greater depressive symptom risk, with stable effects over age and dosage effects for each additional SLE that were smaller than the effects of ECAs among men, but not women. Belonging to an ethnic minority group, having less education, and less household income at baseline were associated with greater depressive symptom risk. Findings suggest the importance of addressing early childhood adversity and sociodemographic factors, among at-risk older adults to mitigate life-course stress proliferative processes and thereby reduce disparate risk for depression in older age.

VL - 26 IS - 4 ER - TY - JOUR T1 - The dynamic association between body mass index and cognition from midlife through late-life, and the effect of sex and genetic influences JF - Scientific Reports Y1 - 2021 A1 - Ida Karlsson A1 - Margaret Gatz A1 - Thalida E. Arpawong A1 - Anna K. Dahl Aslan A1 - Chandra A Reynolds KW - Cognition KW - Epidemiology KW - Genetics KW - longitudinal KW - Obesity AB - Body mass index (BMI) is associated with cognitive abilities, but the nature of the relationship remains largely unexplored. We aimed to investigate the bidirectional relationship from midlife through late-life, while considering sex differences and genetic predisposition to higher BMI. We used data from 23,892 individuals of European ancestry from the Health and Retirement Study, with longitudinal data on BMI and three established cognitive indices: mental status, episodic memory, and their sum, called total cognition. To investigate the dynamic relationship between BMI and cognitive abilities, we applied dual change score models of change from age 50 through 89, with a breakpoint at age 65 or 70. Models were further stratified by sex and genetic predisposition to higher BMI using tertiles of a polygenic score for BMI (PGSBMI). We demonstrated bidirectional effects between BMI and all three cognitive indices, with higher BMI contributing to steeper decline in cognitive abilities in both midlife and late-life, and higher cognitive abilities contributing to less decline in BMI in late-life.&nbsp;The effects of BMI on change in cognitive abilities were more evident in men compared to women, and among those in the lowest tertile of the PGSBMI compared to those in the highest tertile, while the effects of cognition on BMI were similar across groups. In conclusion, these findings highlight a reciprocal relationship between BMI and cognitive abilities, indicating that the negative effects of a higher BMI persist from midlife through late-life, and that weight-loss in late-life may be driven by cognitive decline. VL - 11 SN - 2693-5015 IS - 1 ER - TY - JOUR T1 - Female vulnerability to the effects of smoking on health outcomes in older people JF - PloS one Y1 - 2020 A1 - Haghani, Amin A1 - Thalida E. Arpawong A1 - Jung K Kim A1 - Lewinger, Juan Pablo A1 - Caleb E Finch A1 - Eileen M. Crimmins KW - Cardiovascular disease KW - Smoking KW - Women's Health AB - Cigarette smoking is among the leading risk factors for mortality and morbidity. While men have a higher smoking prevalence, mechanistic experiments suggest that women are at higher risk for health problems due to smoking. Moreover, the comparison of smoking effects on multiple conditions and mortality for men and women has not yet been done in a population-based group with race/ethnic diversity. We used proportional hazards models and restricted mean survival time to assess differences in smoking effects by sex for multiple health outcomes using data from the U.S. Health and Retirement Study (HRS), a population-representative cohort of individuals aged 50+ (n = 22,708, 1992-2014). Men had experienced more smoking pack-years than women (22.0 vs 15.6 average pack-years). Age of death, onset of lung disorders, heart disease, stroke, and cancer showed dose-dependent effects of smoking for both sexes. Among heavy smokers (>28 pack-years) women had higher risk of earlier age of death (HR = 1.3, 95%CI:1.03-1.65) and stroke (HR = 1.37, 95%CI:1.02-1.83). Risk of cancer and heart disease did not differ by sex for smokers. Women had earlier age of onset for lung disorders (HR = 2.83, 95%CI:1.74-4.6), but men risk due to smoking were higher (Smoking-Sex interaction P<0.02) than women. Passive smoke exposure increased risk of earlier heart disease (HR = 1.33, 95%CI:1.07-1.65) and stroke (HR:1.54, 95%CI:1.07-2.22) for non-smokers, mainly in men. Smoking cessation after 15 years partially attenuated the deleterious smoking effects for all health outcomes. In sum, our results suggest that women are more vulnerable to ever smoking for earlier death and risk of stroke, but less vulnerable for lung disorders. From an epidemiological perspective, sex differences in smoking effects are important considerations that could underlie sex differences in health outcomes. These findings also encourage future mechanistic experiments to resolve potential mechanisms of sex-specific cigarette smoke toxicity. VL - 15 SN - 1932-6203 UR - https://pubmed.ncbi.nlm.nih.gov/32497122 IS - 6 U1 - 32497122[pmid] U4 - PONE-D-20-03538[PII] JO - PLoS One ER - TY - JOUR T1 - Resilience Factors That Modify Genetic Risk for ADHD Matter for Later Life Emotional and Cognitive Health Outcomes JF - Innovation in Aging Y1 - 2020 A1 - Thalida E. Arpawong A1 - Milam, Joel KW - ADHD KW - Cognitive health KW - Emotional Health AB - Having features of Attention Deficit Hyperactivity Disorder (ADHD) is associated with challenges with emotional regulation and cognitive function. Heritability for ADHD in adults is estimated to be 30%. The degree to which genetic risk for ADHD can be modified by protective factors, such as strong personal relationships and pursuing more education, to result in better emotional and cognitive outcomes at later ages is not well understood. We evaluated these relationships in a population-representative sample of older adults in the U.S. Health and Retirement Study, with 9,003 European Americans (EA; 57% women, age M=68.6, SD=10.4), and 1,622 African Americans (AA; 63% women, age M=64.4, SD=9.5). Outcomes included validated scales for psychological resilience, life satisfaction, depressive symptoms (DepSx), cognitive functioning, and impairment, assessed between 2008-2012. A genetic risk score for ADHD (GRS-ADHD) was calculated from a genomewide-scan, using a mixed ancestry sample. We used multivariable linear and logistic regression models, adjusted for age, gender, and genetic ancestry. We found a protective effect such that stronger personal relationships in adulthood reduced the inverse relationship between the GRS-ADHD and resilience and life satisfaction in later age (interaction p’s<.004 in EAs), but not with DepSx. In contrast, strong parental relationships in childhood attenuated the association between the GRS-ADHD and later life DepSx (interaction p’s<.007 in EAs and AAs) only. Education did not modify, but mediated the main effect of the GRS-ADHD on cognitive abilities and impairment in EAs and AAs. Findings have implications for later age health for those at greater genetic risk for ADHD. VL - 4 SN - 2399-5300 IS - Suppl 1 ER - TY - JOUR T1 - Comparing the utility of mitochondrial and nuclear DNA to adjust for genetic ancestry in association studies. JF - Cells Y1 - 2019 A1 - Miller, Brendan A1 - Thalida E. Arpawong A1 - Jiao, Henry A1 - Kim, Su-Jeong A1 - Yen, Kelvin A1 - Hemal H Mehta A1 - Wan, Junxiang A1 - John Carpten A1 - Cohen, Pinchas KW - Genetics KW - GWAS KW - Survey Methodology AB - Mitochondrial genome-wide association studies identify mitochondrial single nucleotide polymorphisms (mtSNPs) that associate with disease or disease-related phenotypes. Most mitochondrial and nuclear genome-wide association studies adjust for genetic ancestry by including principal components derived from nuclear DNA, but not from mitochondrial DNA, as covariates in statistical regression analyses. Furthermore, there is no standard when controlling for genetic ancestry during mitochondrial and nuclear genetic interaction association scans, especially across ethnicities with substantial mitochondrial genetic heterogeneity. The purpose of this study is to (1) compare the degree of ethnic variation captured by principal components calculated from microarray-defined nuclear and mitochondrial DNA and (2) assess the utility of mitochondrial principal components for association studies. Analytic techniques used in this study include a principal component analysis for genetic ancestry, decision-tree classification for self-reported ethnicity, and linear regression for association tests. Data from the Health and Retirement Study, which includes self-reported White, Black, and Hispanic Americans, was used for all analyses. We report that (1) mitochondrial principal component analysis (PCA) captures ethnic variation to a similar or slightly greater degree than nuclear PCA in Blacks and Hispanics, (2) nuclear and mitochondrial DNA classify self-reported ethnicity to a high degree but with a similar level of error, and 3) mitochondrial principal components can be used as covariates to adjust for population stratification in association studies with complex traits, as demonstrated by our analysis of height-a phenotype with a high heritability. Overall, genetic association studies might reveal true and robust mtSNP associations when including mitochondrial principal components as regression covariates. VL - 8 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30987182?dopt=Abstract ER - TY - JOUR T1 - Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom. JF - PLoS One Y1 - 2018 A1 - Mekli, Krisztina A1 - Stevens, Adam A1 - Alan Marshall A1 - Thalida E. Arpawong A1 - Drystan F. Phillips A1 - Tampubolon, Gindo A1 - Lee, Jinkook A1 - Carol A Prescott A1 - James Nazroo A1 - Pendleton, Neil KW - ELSA KW - Frailty KW - Gene Ontology KW - Genome-Wide Association Study KW - Phenotype AB -

The concept of frailty has been used in the clinical and research field for more than two decades. It is usually described as a clinical state of heightened vulnerability to poor resolution of homeostasis after a stressor event, which thereby increases the risk of adverse outcomes, including falls, delirium, disability and mortality. Here we report the results of the first genome-wide association scan and comparative gene ontology analyses where we aimed to identify genes and pathways associated with the deficit model of frailty. We used a discovery-replication design with two independent, nationally representative samples of older adults. The square-root transformed Frailty Index (FI) was the outcome variable, and age and sex were included as covariates. We report one hit exceeding genome-wide significance: the rs6765037 A allele was significantly associated with a decrease in the square-root transformed FI score in the Discovery sample (beta = -0.01958, p = 2.14E-08), without confirmation in the Replication sample. We also report a nominal replication: the rs7134291 A allele was significantly associated with a decrease in the square-root transformed FI score (Discovery sample: beta = -0.01021, p = 1.85E-06, Replication sample: beta = -0.005013, p = 0.03433). These hits represent the KBTBD12 and the GRIN2B genes, respectively. Comparative gene ontology analysis identified the pathways 'Neuropathic pain signalling in dorsal horn neurons' and the 'GPCR-Mediated Nutrient Sensing in Enteroendocrine Cells', exceeding the p = 0.01 significance in both samples, although this result does not survive correction for multiple testing. Considering the crucial role of GRIN2B in brain development, synaptic plasticity and cognition, this gene appears to be a potential candidate to play a role in frailty. In conclusion, we conducted genome-wide association scan and pathway analyses and have identified genes and pathways with potential roles in frailty. However, frailty is a complex condition. Therefore, further research is required to confirm our results and more thoroughly identify relevant biological mechanisms.

VL - 13 IS - 11 ER - TY - JOUR T1 - Genome-wide scan of depressive symptomatology in two representative cohorts in the United States and the United Kingdom. JF - Journal of Psychiatric Research Y1 - 2018 A1 - Mekli, Krisztina A1 - Drystan F. Phillips A1 - Thalida E. Arpawong A1 - Vanhoutte, Bram A1 - Tampubolon, Gindo A1 - James Nazroo A1 - Lee, Jinkook A1 - Carol A Prescott A1 - Stevens, Adam A1 - Pendleton, Neil KW - depression KW - ELSA KW - Genome-Wide Association Study AB -

Unlike the diagnosed Major Depressive Disorder, depressive symptomatology in the general population has received less attention in genome-wide association scan (GWAS) studies. Here we report a GWAS study on depressive symptomatology using a discovery-replication design and the following approaches: To improve the robustness of the phenotypic measure, we used longitudinal data and calculated mean scores for at least 3 observations for each individual. To maximize replicability, we used nearly identical genotyping platforms and identically constructed phenotypic measures in both the Discovery and Replication samples. We report one genome-wide significant hit; rs58682566 in the EPG5 gene was associated (p = 3.25E-08) with the mean of the depression symptom in the Discovery sample, without confirmation in the Replication sample. We also report 4 hits exceeding the genome-wide suggestive significance level with nominal replications. Rs11774887, rs4147527 and rs1379328, close to the SAMD12 gene, were associated with the mean depression symptom score (P-values in Discovery sample: 4.58E-06, 7.65E-06 and 7.66E-06; Replication sample: 0.049, 0.029 and 0.030, respectively). Rs13250896, located in an intergenic region, was associated with the mean score of the three somatic items of the depression symptoms score (p = 3.31E-07 and 0.042 for the Discovery and Replication samples). These results were not supported by evidence in the literature. We conclude that despite the strengths of our approach, using robust phenotypic measures and samples that maximize replicability potential, this study does not provide compelling evidence of a single genetic variant's significant role in depressive symptomatology.

VL - 100 ER - TY - JOUR T1 - Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort. JF - PLoS One Y1 - 2017 A1 - Thalida E. Arpawong A1 - Pendleton, Neil A1 - Mekli, Krisztina A1 - John J McArdle A1 - Margaret Gatz A1 - Armoskus, Chris A1 - James A Knowles A1 - Carol A Prescott KW - Cognitive Ability KW - Genetics KW - GWAS KW - Memory AB - Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60. A cognitively intact sample (N = 20,650 with 125,164 observations) was drawn from the U.S. Health and Retirement Study, a nationally representative study of adults aged 50 and older. Mixed effects regression models were constructed using repeated measures from data collected every two years (1996-2012) to estimate level at age 60 and change in memory post-60 in IR and rDR. Genome-wide association scans (GWAS) were conducted in the genotypic subsample (N = 7,486) using ~1.2 million single nucleotide polymorphisms (SNPs). One SNP (rs2075650) in TOMM40 associated with rDR level at the genome-wide level (p = 5.0x10-08), an effect that replicated in an independent sample from the English Longitudinal Study on Ageing (N = 6,898 with 41,328 observations). Meta-analysis of rDR level confirmed the association (p = 5.0x10-11) and identified two others in TOMM40 (rs71352238 p = 1.0x10-10; rs157582 p = 7.0x10-09), and one in APOE (rs769449 p = 3.1 x10-12). Meta-analysis of IR change identified associations with three of the same SNPs in TOMM40 (rs157582 p = 8.3x10-10; rs71352238 p = 1.9x10-09) and APOE (rs769449 p = 2.2x10-08). Conditional analyses indicate GWAS signals on rDR level were driven by APOE, whereas signals on IR change were driven by TOMM40. Additionally, we found that TOMM40 had effects independent of APOE e4 on both phenotypes. Findings from this first U.S. population-based GWAS study conducted on both age-related immediate and delayed verbal memory merit continued examination in other samples and additional measures of verbal memory. VL - 12 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28800603?dopt=Abstract ER - TY - JOUR T1 - Effects of Recent Stress and Variation in the Serotonin Transporter Polymorphism (5-HTTLPR) on Depressive Symptoms: A Repeated-Measures Study of Adults Age 50 and Older. JF - Behavior Genetics Y1 - 2016 A1 - Thalida E. Arpawong A1 - Jinkook Lee A1 - Drystan F. Phillips A1 - Eileen M. Crimmins A1 - Morgan E. Levine A1 - Carol A Prescott KW - Aged KW - Alleles KW - depression KW - Depressive Disorder KW - Ethnic Groups KW - Female KW - Gene-Environment Interaction KW - Genetic Association Studies KW - Genetic Predisposition to Disease KW - Haplotypes KW - Humans KW - Life Change Events KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Promoter Regions, Genetic KW - Serotonin Plasma Membrane Transport Proteins KW - Stress, Psychological AB -

Depending on genetic sensitivity to it, stress may affect depressive symptomatology differentially. Applying the stress-diathesis hypothesis to older adults, we postulate: (1) recent stress will associate with increased depressive symptom levels and (2) this effect will be greater for individuals with at least one short allele of the serotonin transporter gene promoter region (5-HTTLPR). Further, we employ a design that addresses specific limitations of many prior studies that have examined the 5-HTTLPR × SLE relation, by: (a) using a within-person repeated-measures design to address fluctuations that occur within individuals over time, increase power for detecting G × E, and address GE correlation; (b) studying reports of exogenous stressful events (those unlikely to be caused by depression) to help rule out reverse causation and negativity bias, and in order to assess stressors that are more etiologically relevant to depressive symptomatology in older adults. The sample is drawn from the Health and Retirement Study, a U.S. population-based study of older individuals (N = 28,248; mean age = 67.5; 57.3 % female; 80.7 % Non-Hispanic White, 14.9 % Hispanic/Latino, 4.5 % African American; genetic subsample = 12,332), from whom measures of depressive symptoms and exogenous stressors were collected biannually (1994-2010). Variation in the 5-HTTLPR was characterized via haplotype, using two single nucleotide polymorphisms (SNPs). Ordered logit models were constructed to predict levels of depressive symptoms from 5-HTTLPR and stressors, comparing results of the most commonly applied statistical approaches (i.e., comparing allelic and genotypic models, and continuous and categorical predictors) used in the literature. All models were stratified by race/ethnicity. Overall, results show a main effect of recent stress for all ethnic groups, and mixed results for the variation in 5-HTTLPR × stress interaction, contingent upon statistical model used. Findings suggest there may be a differential effect of stressors and 5-HTTLPR on depressive symptoms by ethnicity, but further research is needed, particularly when using a haplotype to characterize variation in 5-HTTLPR in population-based sample with a diverse ethnic composition.

PB - 46 VL - 46 IS - 1 U2 - PMC4720538 U4 - 5-HTTLPR/Depressive symptoms/G/Older adults/Race differences/Stressful life events/Genetic analysis ER - TY - JOUR T1 - A polygenic risk score associated with measures of depressive symptoms among older adults. JF - Biodemography Soc Biol Y1 - 2014 A1 - Morgan E. Levine A1 - Eileen M. Crimmins A1 - Carol A Prescott A1 - Drystan F. Phillips A1 - Thalida E. Arpawong A1 - Jinkook Lee KW - Aged KW - Aged, 80 and over KW - Depressive Disorder, Major KW - Female KW - Genetic Predisposition to Disease KW - Genetic Variation KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Multifactorial Inheritance KW - Odds Ratio KW - Risk Factors AB -

It has been suggested that depression is a polygenic trait, arising from the influences of multiple loci with small individual effects. The aim of this study is to generate a polygenic risk score (PRS) to examine the association between genetic variation and depressive symptoms. Our analytic sample included N = 10,091 participants aged 50 and older from the Health and Retirement Study (HRS). Depressive symptoms were measured by Center for Epidemiological Studies-Depression scale (CESD) scores assessed on up to nine occasions across 18 years. We conducted a genome-wide association analysis for a discovery set (n = 7,000) and used the top 11 single-nucleotide polymorphisms, all with p < 10(-5) to generate a weighted PRS for our replication sample (n = 3,091). Results showed that the PRS was significantly associated with mean CESD score in the replication sample (β = .08, p = .002). The R(2) change for the inclusion of the PRS was .003. Using a multinomial logistic regression model, we also examined the association between genetic risk and chronicity of high (4+) CESD scores. We found that a one-standard-deviation increase in PRS was associated with a 36 percent increase in the odds of having chronically high CESD scores relative to never having had high CESD scores. Our findings are consistent with depression being a polygenic trait and suggest that the cumulative influence of multiple variants increases an individual's susceptibility for chronically experiencing high levels of depressive symptoms.

PB - 60 VL - 60 IS - 2 N1 - Times Cited: 0 SI 0 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25343367?dopt=Abstract U2 - PMC4298361 U4 - GENOME-WIDE ASSOCIATION/INDIVIDUAL GENETIC RISK/MAJOR DEPRESSION/DISEASE RISK/HERITABILITY/genetics/genetics/depression/Depressive Symptoms/CES Depression Scale/CES Depression Scale/regression Analysis ER -