General cognitive ability in high school, attained education, occupational complexity, and dementia risk.

INTRODUCTION: We address the extent to which adolescent cognition predicts dementia risk in later life, mediated by educational attainment and occupational complexity. METHODS: Using data from Project Talent Aging Study (PTAS), we fitted two structural equation models to test whether adolescent cognition predicts cognitive impairment (CI) and Ascertain Dementia 8 (AD8) status simultaneously (NCognitive Assessment = 2477) and AD8 alone (NQuestionnaire = 6491) 60 years later, mediated by education and occupational complexity. Co-twin control analysis examined 82 discordant pairs for CI/AD8. RESULTS: Education partially mediated the effect of adolescent cognition on CI in the cognitive assessment aample and AD8 in the questionnaire sample (Ps < 0.001). Within twin pairs, differences in adolescent cognition were small, but intrapair differences in education predicted CI status. DISCUSSION: Adolescent cognition predicted dementia risk 60 years later, partially mediated through education. Educational attainment, but not occupational complexity, contributes to CI risk beyond its role as a mediator of adolescent cognition, further supported by the co-twin analyses. HIGHLIGHTS: Project Talent Aging Study follows enrollees from high school for nearly 60 years. General cognitive ability in high school predicts later-life cognitive impairment. Low education is a risk partially due to its association with cognitive ability.

High school quality is associated with cognition 58 years later.

We leveraged a unique school-based longitudinal cohort-the Project Talent Aging Study-to examine whether attending higher quality schools is associated with cognitive performance among older adults in the United States (mean age = 74.8). Participants (n = 2,289) completed telephone neurocognitive testing. Six indicators of high school quality, reported by principals at the time of schooling, were predictors of respondents' cognitive function 58 years later. To account for school-clustering, multilevel linear and logistic models were applied. We found that attending schools with a higher number of teachers with graduate training was the clearest predictor of later-life cognition, and school quality mattered especially for language abilities. Importantly, Black respondents (n = 239; 10.5 percentage) were disproportionately exposed to low quality high schools. Therefore, increased investment in schools, especially those that serve Black children, could be a powerful strategy to improve later life cognitive health among older adults in the United States.

Nature, Nurture, and the Meaning of Educational Attainment: Differences by Sex and Socioeconomic Status.

Estimated heritability of educational attainment (EA) varies widely, from 23% to 80%, with growing evidence suggesting the degree to which genetic variation contributes to individual differences in EA is highly dependent upon situational factors. We aimed to decompose EA into influences attributable to genetic propensity and to environmental context and their interplay, while considering influences of rearing household economic status (HES) and sex. We use the Project Talent Twin and Sibling Study, drawn from the population-representative cohort of high school students assessed in 1960 and followed through 2014, to ages 68-72. Data from 3552 twins and siblings from 1741 families were analyzed using multilevel regression and multiple group structural equation models. Individuals from less-advantaged backgrounds had lower EA and less variation. Genetic variance accounted for 51% of the total variance, but within women and men, 40% and 58% of the total variance respectively. Men had stable genetic variance on EA across all HES strata, whereas high HES women showed the same level of genetic influence as men, and lower HES women had constrained genetic influence on EA. Unexpectedly, middle HES women showed the largest constraints in genetic influence on EA. Shared family environment appears to make an outsized contribution to greater variability for women in this middle stratum and whether they pursue more EA. Implications are that without considering early life opportunity, genetic studies on education may mischaracterize sex differences because education reflects different degrees of genetic and environmental influences for women and men.

Postsecondary Education and Late-life Cognitive Outcomes Among Black and White Participants in the Project Talent Aging Study: Can Early-life Cognitive Skills Account for Educational Differences in Late-life Cognition?

BACKGROUND: Higher education consistently predicts improved late-life cognition. Racial differences in educational attainment likely contribute to inequities in dementia risk. However, few studies of education and cognition have controlled for prospectively measured early-life confounders or evaluated whether the education late-life cognition association is modified by race/ethnicity. METHODS: Among 2343 Black and White Project Talent Aging Study participants who completed telephone cognitive assessments, we evaluated whether the association between years of education and cognition (verbal fluency, memory/recall, attention, and a composite cognitive measure) differed by race, and whether these differences persisted when adjusting for childhood factors, including the cognitive ability. RESULTS: In fully adjusted linear regression models, each additional year of education was associated with higher composite cognitive scores for Black [ß=0.137; 95% confidence interval (CI)=0.068, 0.206] and White respondents (ß=0.056; CI=0.034, 0.078) with an interaction with race ( P =0.03). Associations between education and memory/recall among Black adults (ß=0.036; CI=-0.037, 0.109) and attention among White adults (ß=0.022; CI=-0.002, 0.046) were nonsignificant. However, there were significant race-education interactions for the composite ( P =0.03) and attention measures ( P <0.001) but not verbal fluency ( P =0.61) or memory/recall ( P =0.95). CONCLUSION: Education predicted better overall cognition for both Black and White adults, even with stringent control for prospectively measured early-life confounders.

Financial strain moderates genetic influences on self-rated health: support for diathesis-stress model of gene-environment interplay.

Data from the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium were used to examine predictions of different models of gene-by-environment interaction to understand how genetic variance in self-rated health (SRH) varies at different levels of financial strain. A total of 11,359 individuals from 10 twin studies in Australia, Sweden, and the United States contributed relevant data, including 2,074 monozygotic and 2,623 dizygotic twin pairs. Age ranged from 22 to 98 years, with a mean age of 61.05 (SD = 13.24). A factor model was used to create a harmonized measure of financial strain across studies and items. Twin analyses of genetic and environmental variance for SRH incorporating age, age2, sex, and financial strain moderators indicated significant financial strain moderation of genetic influences on self-rated health. Moderation results did not differ across sex or country. Genetic variance for SRH increased as financial strain increased, matching the predictions of the diathesis-stress and social comparison models for components of variance. Under these models, environmental improvements would be expected to reduce genetically based health disparities.

A longitudinal study shows stress proliferation effects from early childhood adversity and recent stress on risk for depressive symptoms among older adults.

Objectives: 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.Method: 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: 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.Conclusions: 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.

IGEMS: The Consortium on Interplay of Genes and Environment Across Multiple Studies - An Update.

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene-environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14-103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.

The Project Talent Twin and Sibling Study: Zygosity and New Data Collection.

The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942-1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9-12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the 'common' environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with school/community-level factors. We term this the GIFTS model for genetics, individual, family, twin, and school sources of variance. In our article published in a previous Twin Research and Human Genetics special issue, we described data collections conducted with the full Project Talent sample during 1960-1974, methods for the recent linking of siblings within families, identification of twins, and the design of a 54-year follow-up of the PTTS sample, when participants were 68-72 years old. In the current article, we summarize participation and data available from this 2014 collection, describe our method for assigning zygosity using survey responses and yearbook photographs, illustrate the GIFTS model applied to 1960 vocabulary scores from more than 80,000 adolescent twins, siblings and schoolmates and summarize the next wave of PTTS data collection being conducted as part of the larger Project Talent Aging Study.

Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom.

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.

Genome-wide scan of depressive symptomatology in two representative cohorts in the United States and the United Kingdom.

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.

Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort.

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.

Latent classes of alcohol problems in Mauritian men: Results from the Joint Child Health Project.

INTRODUCTION AND AIMS: The purpose of this study was to identify latent classes of alcohol problems and their sociodemographic correlates in the east African nation of Mauritius. DESIGN AND METHODS: Participants were from the Joint Child Health Project, a longitudinal study of a 1969-1970 birth cohort of 1795 individuals. In mid-adulthood (M = 37 years), all available participants (n = 1206; 67% of the original cohort) were assessed for demographic characteristics, and lifetime drinkers were assessed for alcohol-related problems. Given the low endorsement of problems by women, only male lifetime drinkers (n = 520) were included in the latent class analyses. RESULTS: Analyses indicated the best-fitting model contained four classes of drinkers: Non-problematic (66%), Moderate (16%), Hazardous (11%) and Severe (6%). Lower education and occupation were associated with Moderate and Severe problem classes, whereas higher education and occupation were associated with the Hazardous class. Being Hindu, Tamil and Creole were differentially predictive of class membership, but being Muslim was not. DISCUSSION AND CONCLUSIONS: Our findings provide evidence of a distinct Hazardous drinking class that has unique demographic correlates and may represent a cluster of problems that is more bound by cultural factors. We also found problem classes on a severity continuum from none to moderate to severe problems. This study highlights the importance of examining societal, subgroup and person-level factors to produce a more nuanced understanding of distinct classes of alcohol-related problems. [Luczak SE, Prescott CA, Venables PH. Latent classes of alcohol problems in Mauritian men: Results from the Joint Child Health Project.

Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms.

BACKGROUND: Alcohol dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1,748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms (MOs) to assess the role of orthologous genes in ethanol (EtOH)-response behaviors. We tested 1 primate-specific gene for expression differences in case/control postmortem brain tissue. RESULTS: We detected significant association in COL6A3 and suggestive association in 2 previously implicated loci, KLF12 and RYR3. None of these signals are significant in replication. A suggestive signal in the long noncoding RNA LOC339975 is significant in case:control meta-analysis, but not in a population sample. Knockdown of a COL6A3 ortholog in Caenorhabditis elegans reduced EtOH sensitivity. Col6a3 expression correlated with handling-induced convulsions in mice. Loss of function of the KLF12 ortholog in C. elegans impaired development of acute functional tolerance (AFT). Klf12 expression correlated with locomotor activation following EtOH injection in mice. Loss of function of the RYR3 ortholog reduced EtOH sensitivity in C. elegans and rapid tolerance in Drosophila. The ryanodine receptor antagonist dantrolene reduced motivation to self-administer EtOH in rats. Expression of LOC339975 does not differ between cases and controls but is reduced in carriers of the associated rs11726136 allele in nucleus accumbens (NAc). CONCLUSIONS: We detect association between AD and COL6A3, KLF12, RYR3, and LOC339975. Despite nonreplication of COL6A3, KLF12, and RYR3 signals, orthologs of these genes influence behavioral response to EtOH in MOs, suggesting potential involvement in human EtOH response and AD liability. The associated LOC339975 allele may influence gene expression in human NAc. Although the functions of long noncoding RNAs are poorly understood, there is mounting evidence implicating these genes in multiple brain functions and disorders.

Anxiety trajectories in the second half of life: Genetic and environmental contributions over age.

Clinically significant anxiety symptoms are prevalent among the elderly, yet knowledge about the longitudinal course of anxiety symptoms in later life remains scarce. The goals of this study were to (a) characterize age trajectories of state anxiety symptoms in the second half of life, and (b) estimate genetic and environmental contributions to individual differences in the age trajectory of state anxiety. This study was based on data from 1,482 participants in the Swedish Adoption/Twin Study of Aging who were aged 50 and older at their first occasion (512 complete twin pairs, 458 singletons) and had up to 6 measurement occasions spanning 11 years. Consistent with life span developmental theories of age-related emotional change, anxiety symptom levels declined during the transition from midlife to the mid-60s, followed by a mild increase that gradually plateaued in the 80s. There were substantial individual differences in the age trajectory of anxiety. After accounting for effects of sex, cohort, mode of testing, and proximity to death, this longitudinal variation was partitioned into biometric sources. Nonshared environmental variance was highest in the late 60s and declined thereafter, whereas genetic variance increased at an accelerated pace from approximately age 60 onward. There was no evidence for effects of rearing or other shared environment on anxiety symptoms in later life. These findings highlight how the etiology of anxiety symptoms changes from midlife to old age.

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.

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.

Childhood cognitive measures as predictors of alcohol use and problems by mid-adulthood in a non-Western cohort.

This study examined the relationship between childhood cognitive functioning and academic achievement and subsequent alcohol use and problems in a non-Western setting. We examined longitudinal data from a birth cohort sample (N = 1,795) who were assessed at age 11 years on cognitive measures and then approximately 25 years later on lifetime alcohol use and alcohol use disorder symptom count. The sample was from Mauritius (eastern Africa), which allowed us to examine these relationships in a non-Western society with a different social structure than is typical of prior cognitive studies on primarily White samples in Western societies. Poorer performance on the Trail Making Test B-A in childhood predicted being a lifetime drinker, even after covarying for gender, childhood psychosocial adversity, and Muslim religion. Lower academic achievement and verbal IQ, but not performance IQ, were predictive of subsequent alcohol problems after including demographic covariates; the relationship between verbal IQ and alcohol problems was stronger in females than males. A nonlinear relationship emerged for Trails, suggesting that only more extreme impairment on this measure was indicative of later alcohol problems. Results of this study provide evidence that verbal deficits and poor academic performance exist in a general cohort sample by age 11 years (when 99% were nondrinkers) for those who go on to develop alcohol problems. (PsycINFO Database Record

Multiple mechanisms influencing the relationship between alcohol consumption and peer alcohol use.

BACKGROUND: Alcohol consumption is typically correlated with the alcohol use behaviors of one's peers. Previous research has suggested that this positive relationship could be due to social selection, social influence, or a combination of both processes. However, few studies have considered the role of shared genetic and environmental influences in conjunction with causal processes. METHODS: This study uses data from a sample of male twins (N = 1,790) who provided retrospective reports of their own alcohol consumption and their peers' alcohol-related behaviors, from adolescence into young adulthood (ages 12 to 25). Structural equation modeling was employed to compare 3 plausible models of genetic and environmental influences on the relationship between phenotypes over time. RESULTS: Model fitting indicated that one's own alcohol consumption and the alcohol use of one's peers are related through both genetic and shared environmental factors and through unique environmental causal influences. The relative magnitude of these factors, and their contribution to covariation, changed over time, with genetic factors becoming more meaningful later in development. CONCLUSIONS: Peers' alcohol use behaviors and one's own alcohol consumption are related through a complex combination of genetic and environmental factors that act via correlated factors and the complementary causal mechanisms of social selection and influence. Understanding these processes can inform risk assessment as well as improve our ability to model the development of alcohol use.

Drinking experience uncovers genetic influences on alcohol expectancies across adolescence.

AIMS: To test whether drinking onset moderates genetic and environmental contributions to individual differences in the etiology of alcohol expectancies across adolescence. DESIGN: Longitudinal twin design. SETTING: Community sample from Los Angeles, CA, USA. PARTICIPANTS: A total of 1292 male and female twins, aged 11­18years, were assessed at 1 (n = 440), 2 (n = 587) or 3 (n = 265) occasions as part of the risk factors for the Antisocial Behavior Twin Study. MEASUREMENTS: Social behavioral (SB) alcohol expectancies were measured using an abbreviated version of the Social Behavioral subscale from the Alcohol Expectancy Questionnaire for adolescents (AEQ-A). Drinking onset was defined as >1 full drink of alcohol. FINDINGS: Alcohol expectancies increased over age and the increase became more rapid following onset of drinking. The importance of genetic and environmental influences on SB scores varied with age and drinking status, such that variation prior to drinking onset was attributed solely to environmental influences, whereas all post-onset variation was attributed to genetic influences. Results did not differ significantly by sex. CONCLUSION: Only environmental factors explain beliefs about the social and behavioral consequences of alcohol use prior to drinking onset,whereas genetic factors explain an increasing proportion of the variance in these beliefs after drinking onset.

A polygenic risk score associated with measures of depressive symptoms among older adults.

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 (ß = .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.

Effects of ALDH2∗2 on alcohol problem trajectories of Asian American college students.

The variant aldehyde dehydrogenase allele, ALDH2∗2, consistently has been associated with protection against alcohol dependence, but the mechanism underlying this process is not known. This study examined growth trajectories of alcohol consumption (frequency, average quantity, binge drinking, maximum drinks) and problems over the college years and then tested whether the ALDH2 genotype mediated or moderated the relationship between alcohol consumption and problems. Asian American college students (N = 433) reported on their drinking behavior in their first year of college and then annually for 3 consecutive years. Alcohol consumption and problems increased over the college years for both those with and without ALDH2∗2, but having an ALDH2∗2 allele was associated with less of an increase in problems over time. A mediation model was supported, with ALDH2∗2 group differences in problems fully accounted for by differences in frequency of binge drinking. Findings also supported a moderation hypothesis: All four alcohol consumption variables were significant predictors of subsequent alcohol problems, but these relationships were not as strong in those with ALDH2∗2 as in those without ALDH2∗2. Our findings suggest that the interplay between ALDH2∗2 and drinking-related problems is complex, involving both mediation and moderation processes that reduce the likelihood of developing problems via reduction of heavy drinking as well as by altering the relationship between alcohol consumption and problems. Results of this longitudinal study provide evidence that what seems like a relatively straightforward effect of a diminished ability to metabolize alcohol on drinking behavior is actually dependent on behavior and developmental stage.