Assessment of genetic and nongenetic interactions for the prediction of depressive symptomatology: an analysis of the Wisconsin Longitudinal Study using machine learning algorithms.

OBJECTIVES: We examined depression within a multidimensional framework consisting of genetic, environmental, and sociobehavioral factors and, using machine learning algorithms, explored interactions among these factors that might better explain the etiology of depressive symptoms. METHODS: We measured current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (n = 6378 participants in the Wisconsin Longitudinal Study). Genetic factors were 78 single nucleotide polymorphisms (SNPs); environmental factors-13 stressful life events (SLEs), plus a composite proportion of SLEs index; and sociobehavioral factors-18 personality, intelligence, and other health or behavioral measures. We performed traditional SNP associations via logistic regression likelihood ratio testing and explored interactions with support vector machines and Bayesian networks. RESULTS: After correction for multiple testing, we found no significant single genotypic associations with depressive symptoms. Machine learning algorithms showed no evidence of interactions. Naïve Bayes produced the best models in both subsets and included only environmental and sociobehavioral factors. CONCLUSIONS: We found no single or interactive associations with genetic factors and depressive symptoms. Various environmental and sociobehavioral factors were more predictive of depressive symptoms, yet their impacts were independent of one another. A genome-wide analysis of genetic alterations using machine learning methodologies will provide a framework for identifying genetic-environmental-sociobehavioral interactions in depressive symptoms.

Most reported genetic associations with general intelligence are probably false positives.

General intelligence (g) and virtually all other behavioral traits are heritable. Associations between g and specific single-nucleotide polymorphisms (SNPs) in several candidate genes involved in brain function have been reported. We sought to replicate published associations between g and 12 specific genetic variants (in the genes DTNBP1, CTSD, DRD2, ANKK1, CHRM2, SSADH, COMT, BDNF, CHRNA4, DISC1, APOE, and SNAP25) using data sets from three independent, well-characterized longitudinal studies with samples of 5,571, 1,759, and 2,441 individuals. Of 32 independent tests across all three data sets, only 1 was nominally significant. By contrast, power analyses showed that we should have expected 10 to 15 significant associations, given reasonable assumptions for genotype effect sizes. For positive controls, we confirmed accepted genetic associations for Alzheimer's disease and body mass index, and we used SNP-based calculations of genetic relatedness to replicate previous estimates that about half of the variance in g is accounted for by common genetic variation among individuals. We conclude that the molecular genetics of psychology and social science requires approaches that go beyond the examination of candidate genes.

Does Psychological Well-Being Change with Age?: Longitudinal Tests of Age Variations and Further Exploration of the Multidimensionality of Ryff's Model of Psychological Well-Being.

Using two population-based surveys, we provide the first test of longitudinal age variations in Ryff's scales of psychological well-being (RPWB) across three midlife to later-life transitions. Through these analyses we explore: (a) age variation in RPWB, (b) the structure of RPWB, and (c) the potential for methodologically driven age patterns. In general, RPWB dimensions do not consistently exhibit distinct age profiles; further, longitudinal age variations are exceptionally small, never accounting for more than four percent of the variance. We observe far greater variation within ages or periods than between subscales across age or time - providing strong evidence against substantively different age profiles of RPWB. Moreover, heterogeneity among positively and negatively worded items yield varied age patterns indicating that age variations of RWPB could be driven, at least in part, by methodological artifacts rather than maturation.

Explaining the gender wealth gap.

To assess and explain the United States' gender wealth gap, we use the Wisconsin Longitudinal Study to examine wealth accumulated by a single cohort over 50 years by gender, by marital status, and limited to the respondents who are their family's best financial reporters. We find large gender wealth gaps between currently married men and women, and between never-married men and women. The never-married accumulate less wealth than the currently married, and there is a marital disruption cost to wealth accumulation. The status-attainment model shows the most power in explaining gender wealth gaps between these groups explaining about one-third to one-half of the gap, followed by the human-capital explanation. In other words, a lifetime of lower earnings for women translates into greatly reduced wealth accumulation. After controlling for the full model, we find that a gender wealth gap remains between married men and women that we speculate may be related to gender differences in investment strategies and selection effects.

Hypothalamic-pituitary-gonadal axis homeostasis predicts longevity.

The reproductive-cell cycle theory of aging posits that reproductive hormone changes associated with menopause and andropause drive senescence via altered cell cycle signaling. Using data from the Wisconsin Longitudinal Study (n = 5,034), we analyzed the relationship between longevity and menopause, including other factors that impact "ovarian lifespan" such as births, oophorectomy, and hormone replacement therapy. We found that later onset of menopause was associated with lower mortality, with and without adjusting for additional factors (years of education, smoking status, body mass index, and marital status). Each year of delayed menopause resulted in a 2.9% reduction in mortality; after including a number of additional controls, the effect was attenuated modestly but remained statistically significant (2.6% reduction in mortality). We also found that no other reproductive parameters assessed added to the prediction of longevity, suggesting that reproductive factors shown to affect longevity elsewhere may be mediated by age of menopause. Thus, surgical and natural menopause at age 40, for example, resulted in identical survival probabilities. These results support the maintenance of the hypothalamic-pituitary-gonadal axis in homeostasis in prolonging human longevity, which provides a coherent framework for understanding the relationship between reproduction and longevity.

Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study.

OBJECTIVES: Single genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene-gene (G × G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and age-related diseases would identify significant interactions with increased predictive power for depression. DESIGN: A retrospective cohort study. SETTING: A survey of participants in the Wisconsin Longitudinal Study. PARTICIPANTS: A total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white. PRIMARY OUTCOME MEASURE: Depression as determine by the Composite International Diagnostic Interview-Short-Form. RESULTS: Using a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G × G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G × G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) → (after): men: GNRH1 novel SNP: (1.43 → 1.57); women: APOC3 rs2854116: (1.28 → 1.55), ACVR2B rs3749386: (1.11 → 2.17), FTO rs1421085: (1.32 → 1.65), IL6 rs1800795: (1.12 → 1.85)). CONCLUSIONS: The results suggest that examining G × G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1 and DRD2) and neuroendocrine (GNRH1 and ACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology.

The Promises and Pitfalls of Genoeconomics*

This article reviews existing research at the intersection of genetics and economics, presents some new findings that illustrate the state of genoeconomics research, and surveys the prospects of this emerging field. Twin studies suggest that economic outcomes and preferences, once corrected for measurement error, appear to be about as heritable as many medical conditions and personality traits. Consistent with this pattern, we present new evidence on the heritability of permanent income and wealth. Turning to genetic association studies, we survey the main ways that the direct measurement of genetic variation across individuals is likely to contribute to economics, and we outline the challenges that have slowed progress in making these contributions. The most urgent problem facing researchers in this field is that most existing efforts to find associations between genetic variation and economic behavior are based on samples that are too small to ensure adequate statistical power. This has led to many false positives in the literature. We suggest a number of possible strategies to improve and remedy this problem: (a) pooling data sets, (b) using statistical techniques that exploit the greater information content of many genes considered jointly, and (c) focusing on economically relevant traits that are most proximate to known biological mechanisms.

Adolescent IQ and survival in the Wisconsin longitudinal study.

OBJECTIVE: This study attempts to explain the ubiquitous positive correlation between cognitive ability (IQ) and survival. METHODS: A sample of 10,317 Wisconsin high school graduates of 1957 was followed until 2009, from ages 18 to 68 years. Mortality was analyzed using a Weibull survival model that includes gender, social background, Henmon-Nelson IQ, and rank in high school class. RESULTS: Rank in high school class, a cumulative measure of responsible performance during high school, entirely mediates the relationship between adolescent IQ and survival. Its effect on survival is 3 times greater than that of IQ, and it accounts for about 10% of the female advantage in survival. DISCUSSION: Cognitive functioning may improve survival by promoting responsible and timely patterns of behavior that are firmly in place by late adolescence. Prior research suggests that conscientiousness, one of the "Big Five" personality characteristics, plays a key role in this relationship.

Using anchoring vignettes to assess group differences in general self-rated health.

This article addresses a potentially serious problem with the widely used self-rated health (SRH) survey item: that different groups have systematically different ways of using the item's response categories. Analyses based on unadjusted SRH may thus yield misleading results. The authors evaluate anchoring vignettes as a possible solution to this problem. Using vignettes specifically designed to calibrate the SRH item and data from the Wisconsin Longitudinal Study (WLS; N = 2,625), the authors show how demographic and health-related factors, including sex and education, predict differences in rating styles. Such differences, when not adjusted for statistically, may be sufficiently large to lead to mistakes in rank orderings of groups. In the present sample, unadjusted models show that women have better SRH than men, but this difference disappears in models adjusting for women's greater health-optimism. Anchoring vignettes appear a promising tool for improving intergroup comparability of SRH.

Precarious employment, bad jobs, labor unions, and early retirement.

OBJECTIVES: We examined the extent to which involuntary job loss, exposure to "bad jobs," and labor union membership across the life course are associated with the risk of early retirement. METHODS: Using data from the Wisconsin Longitudinal Study, a large (N=8,609) sample of men and women who graduated from high school in 1957, we estimated discrete-time event history models for the transition to first retirement through age 65. We estimated models separately for men and women. RESULTS: We found that experience of involuntary job loss and exposure to bad jobs are associated with a lower risk of retiring before age 65, whereas labor union membership is associated with a higher likelihood of early retirement. These relationships are stronger for men than for women and are mediated to some extent by pre-retirement differences in pension eligibility, wealth, job characteristics, and health. DISCUSSION: Results provide some support for hypotheses derived from theories of cumulative stratification, suggesting that earlier employment experiences should influence retirement outcomes indirectly through later-life characteristics. However, midlife employment experiences remain associated with earlier retirement, net of more temporally proximate correlates, highlighting the need for further theorization and empirical evaluation of the mechanisms through which increasingly common employment experiences influence the age at which older Americans retire.

Causes and Consequences of Cognitive Functioning Across the Life Course.

Research on variation in cognitive abilities has focused largely on their genetic or experiential sources and on their economic consequences. This article takes a broader look at the consequences of cognitive ability-IQ-across the life course. Contrary to received wisdom, the effects of IQ on economic success are almost entirely mediated by educational attainment. Among persons with equal levels of schooling, IQ has little influence on job performance, occupational standing, earnings, or wealth. But there are other, sometimes surprising consequences of IQ throughout adult life. The long-term correlates of adolescent cognition include drinking behavior, survey participation, Internet use, and the timing of menopause. These are surveyed primarily using findings from the Wisconsin Longitudinal Study.

Recent developments in longitudinal studies of aging in the United States.

We review recent developments in longitudinal studies of aging, focusing on the Wisconsin Longitudinal Study (WLS) and the Health and Retirement Study (HRS). Both studies are part of a trend toward biosocial surveys in which biological measurement is joined with traditional survey techniques, and a related trend toward greater harmonization across studies. Both studies have collected DNA samples and are working toward genotyping that would allow broadly based association studies. Increased attention to psychological measurement of personality and of cognitive ability using adaptive testing structures has also been shared across the studies. The HRS has expanded its economic measurement to longitudinal studies of consumption and to broader-based measurement of pension and Social Security wealth. It has added biomarkers of cardiovascular risk. The WLS has developed an integrated approach to the study of death and bereavement and an innovative use of high school yearbook photographs to capture information about health in early life of its participants.

Later-life Employment Preferences and Outcomes: The Role of Mid-life Work Experiences.

In this paper, we evaluate relationships between mid-life work experiences and the realization of preferences for full-time employment, part-time employment, and complete retirement at age 63-64. Using rich data from the Wisconsin Longitudinal Study, we demonstrate that the likelihood of achieving one's preferred employment status is related to earlier work experiences including employment stability in mid-life and self-employment, part-time employment, and private pension coverage across the life course. Despite large gender differences in work experiences across the life course, relationships between earlier work experiences and the likelihood of realizing later-life employment preferences are generally similar for men and women. We also find that these relationships are only partially mediated by economic and employment circumstances in late mid-life, suggesting the need for further evaluation of the cumulative pathways linking mid-life work experiences to the realization of later-life employment preferences.

Do birth cohorts matter? Age-period-cohort analyses of the obesity epidemic in the United States.

Many studies have cited the importance of secular changes or "period effects" as causes of the U.S. obesity epidemic. Unfortunately, relatively little attention has been devoted to the possible influence of cohort-related mechanisms. To address this current gap in the scientific literature, this investigation utilized the responses from 1.7 million participants in the 1976-2002 National Health Interview Surveys to determine how birth cohorts may have contributed to the rapid increase in the prevalence of obesity. Results from hierarchical age-period-cohort (HAPC) models confirmed that period effects are principally responsible for the U.S. obesity epidemic. However, HAPC models also demonstrated that birth cohort membership is influential. Independent of age and period effects, the predicted probability of obesity at age 25 increased by 30% for cohorts born between 1955 and 1975. Our results also showed that age, period and cohort effects varied by race/gender and educational attainment. For instance, increases in the predicted probabilities of obesity were particularly sharp for recent cohorts of Black females. Our investigation successfully demonstrated that both secular change and birth cohort membership have independently contributed to elevated odds of obesity among recent generations of Americans, suggesting that cohort-specific strategies may be needed to combat disconcertingly high rates of obesity in the U.S.

Do Older Adults Know Their Spouses' End-of-Life Treatment Preferences?

When terminally ill patients become mentally incapacitated, the patient's surrogate often makes treatment decisions in collaboration with health care providers. We examine how surrogates' errors in reporting their spouse's preferences are affected by their gender, status as durable power of attorney for health care (DPAHC), whether the surrogate and spouse held discussions about end-of-life preferences, and the spouse's health status. We apply structural equation models to data from 2,750 married couples in their mid 60s who participated in the 2004 wave of the Wisconsin Longitudinal Study. Surrogates reported their spouse's preferences incorrectly 13 and 26 percent of the time in end-of-life scenarios involving cognitive impairment and physical pain, respectively. Surrogates projected their own preferences onto the spouse. Similar patterns emerged regardless of surrogate gender, surrogate status as DPAHC, marital discussions about end-of-life, or spousal health status. We discuss implications for the process of surrogate decision-making and for future research.

Predicting adult health and mortality from adolescent facial characteristics in yearbook photographs.

Several important longitudinal studies in the social sciences have omitted biomarkers that are routinely recorded today, including height and weight. To account for this shortcoming in the Wisconsin Longitudinal Study (WLS), an 11-point scale was developed to code high school senior class yearbook photographs of WLS participants for relative body mass (RBM). Our analyses show that although imperfect, the RBM scale is reliable (alpha = .91) and meets several criteria of validity as a measure of body mass. Measured at ages 17-18, the standardized relative body mass index (SRBMI) was moderately correlated (r = .31) with body mass index (BMI) at ages 53-54 and with maximum BMI reported between ages 16 and 30 (r = .48). Overweight adolescents (> or = 90th percentile of SRBMI) were about three times more likely than healthy-weight adolescents (10th-80th percentile of SRBMI) to be obese in adulthood and, as a likely consequence, significantly more likely to report health problems such as chest pain and diabetes. Overweight adolescents also suffered a twofold risk of premature death from all nonaccidental causes as well as a fourfold risk of heart disease mortality. The RBM scale has removed a serious obstacle to obesity research and lifelong analyses of health in the WLS. We suggest that other longitudinal studies may also be able to obtain photos of participants at younger ages and thus gain a prospectively useful substitute for direct measures of body mass.

Have we put an end to social promotion? Changes in school progress among children aged 6 to 17 from 1972 to 2005.

We examine trends over time in the proportion of children below the modal grade for their age (BMG), a proxy for grade retention, and in the effects of its demographic and socioeconomic correlates. We estimate a logistic regression model with partial constraints predicting BMG using the annual October school enrollment supplements of the Current Population Survey This model identifies systematic variation in the effects of social background across age and time from 1972 to 2005. While the effects of socioeconomic background variables on progress through school have become increasingly powerful as children grow older that typical pattern has been attenuated across the past three decades by a steady secular decline in the influence of those variables across all ages. A great deal of concern has been expressed about rising levels of economic and social inequality in the United States since the middle 1970s, and about the potential intergenerational effects of such inequality. However, there has been an opposite trend in the effects of social origins on being BMG. A trend is not a law, and there is reason to be concerned about the recent deceleration of the secular decline in effects of social background on being BMG.