Genetic analysis of social-class mobility in five longitudinal studies.

A summary genetic measure, called a "polygenic score," derived from a genome-wide association study (GWAS) of education can modestly predict a person's educational and economic success. This prediction could signal a biological mechanism: Education-linked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents' position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother's polygenic score predicted her child's attainment over and above the child's own polygenic score, suggesting parents' genetics can also affect their children's attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals' family-of-origin environments and their social mobility.

The Implications of Unintended Pregnancies for Mental Health in Later Life.

Despite decades of research on unintended pregnancies, we know little about the health implications for the women who experience them. Moreover, no study has examined the implications for women whose pregnancies occurred before Roe v. Wade was decided--nor whether the mental health consequences of these unintended pregnancies continue into later life. Using the Wisconsin Longitudinal Study, a 60-year ongoing survey, we examined associations between unwanted and mistimed pregnancies and mental health in later life, controlling for factors such as early life socioeconomic conditions, adolescent IQ, and personality. We found that in this cohort of mostly married and White women, who completed their pregnancies before the legalization of abortion, unwanted pregnancies were strongly associated with poorer mental health outcomes in later life.

Associations Between Midlife Menopausal Hormone Therapy Use, Incident Diabetes, and Late Life Memory in the Wisconsin Longitudinal Study.

BACKGROUND: Prior research suggests a link between menopausal hormone therapy (MHT) use, memory function, and diabetes risk. The menopausal transition is a modifiable period to enhance long-term health and cognitive outcomes, although studies have been limited by short follow-up periods precluding a solid understanding of the lasting effects of MHT use on cognition. OBJECTIVE: We examined the effects of midlife MHT use on subsequent diabetes incidence and late life memory performance in a large, same-aged, population-based cohort. We hypothesized that the beneficial effects of MHT use on late life cognition would be partially mediated by reduced diabetes risk. METHODS: 1,792 women from the Wisconsin Longitudinal Study (WLS) were included in analysis. We employed hierarchical linear regression, Cox regression, and causal mediation models to test the associations between MHT history, diabetes incidence, and late life cognitive performance. RESULTS: 1,088/1,792 women (60.7%) reported a history of midlife MHT use and 220/1,792 (12.3%) reported a history of diabetes. MHT use history was associated with better late life immediate recall (but not delayed recall), as well as a reduced risk of diabetes with protracted time to onset. Causal mediation models suggest that the beneficial effect of midlife MHT use on late life immediate recall were at least partially mediated by diabetes risk. CONCLUSION: Our data support a beneficial effect of MHT use on late life immediate recall (learning) that was partially mediated by protection against diabetes risk, supporting MHT use in midlife as protective against late life cognitive decline and adverse health outcomes.

Using sibling models to unpack the relationship between education and cognitive functioning in later life.

As the population ages and the prevalence of dementia increases, unpacking robust and persistent associations between educational attainment and later life cognitive functioning is increasingly important. We do know, from studies with robust causal designs, that policies that increase years of schooling improve later life cognitive functioning. Yet these studies don't illuminate why older adults with greater educational attainment have relatively preserved cognitive functioning. Studies focused on why, however, have been hampered by methodological limitations and inattention to some key explanations for this relationship. Consequently, we test explanations encompassing antecedent factors, specifically family environments, adolescent IQ, and genetic factors, as well as adult mediating mechanisms, specifically health behaviors and health. We employ the Wisconsin Longitudinal Study, which includes 80 years of prospectively collected data on a sample of 1 in every 3 high school graduates, and a selected sibling, from the class of 1957. Sibling models, and the inclusion of prospectively collected early and midlife covariates, allows us to address the explanatory and methodological limitations of the prior literature to better unpack the relationship between education and later life cognitive functioning. We find little evidence that early life genetic endowments and environments, or midlife health and health behaviors, explain the relationship. Adolescent cognition, however, does matter; higher educational attainment, linked to antecedent adolescent cognitive functioning, helps protect against lower levels of cognitive functioning in later life. Both adolescent cognition and education, however, independently associate with later life cognitive functioning at relatively similar magnitudes. Educational attainment's relationship to later life cognitive functioning is not simply a function of adolescent cognitive functioning.

Does Rural Living in Early Life Increase the Risk for Reduced Cognitive Functioning in Later Life?

BACKGROUND: There is a robust consensus, most recently articulated in the 2020 Lancet Commission, that the roots of dementia can be traced to early life, and that the path to prevention may start there as well. Indeed, a growing body of research demonstrates that early life disadvantage may influence the risk for later life dementia and cognitive decline. A still understudied risk, however, is early life rural residence, a plausible pathway given related economic and educational disadvantages, as well as associations between later life rural living and lower levels of cognitive functioning. OBJECTIVE: We aim to examine whether living in rural environments during early life has long term implications for cognitive health in later life. METHODS: We employed the Wisconsin Longitudinal Study, which tracked 1 in every 3 high school graduates from the class of 1957, from infancy to ∼age 72. The data include a rich array of prospectively collected early life data, unique among existing studies, as well as later life measures of cognitive functioning. RESULTS: We found a robust relationship between early life rural residence, especially living on a farm, and long-term risk for reduced cognitive performance on recall and fluency tasks. Controls for adolescent cognitive functioning, APOEɛ2 and APOEɛ4, as well as childhood and adult factors, ranging from early life socioeconomic conditions to later life health and rural and farm residency, did not alter the findings. CONCLUSION: Rural living in early life is an independent risk for lower levels of cognitive functioning in later life.

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10-17), arthritis (GDF5 p = 4 × 10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.

Mutation goals in the vitamin D receptor predicted by computational methods.

The mechanism through which nuclear receptors respond differentially to structurally distinct agonists is a poorly understood process. We present a computational method that identifies nuclear receptor amino acids that are likely involved in biological responses triggered by ligand binding. The method involves tracing how structural changes spread from the ligand binding pocket to the sites on the receptor surface, which makes it a good tool for studying allosteric effects. We employ the method to the vitamin D receptor and verify that the identified amino acids are biologically relevant using a broad range of experimental data and a genome browser. We infer that surface vitamin D receptor residues K141, R252, I260, T280, T287 and L417 are likely involved in cell differentiation and antiproliferation, whereas P122, D149, K321, E353 and Q385 are linked to carcinogenesis.

Schools as Moderators of Genetic Associations with Life Course Attainments: Evidence from the WLS and Add Health.

Genetic variants identified in genome-wide association studies of educational attainment have been linked with a range of positive life course development outcomes. However, it remains unclear whether school environments may moderate these genetic associations. We analyze data from two biosocial surveys that contain both genetic data and follow students from secondary school through mid- to late life. We test if the magnitudes of the associations with educational and occupational attainments varied across the secondary schools that participants attended or with characteristics of those schools. Although we find little evidence that genetic associations with educational and occupational attainment varied across schools or with school characteristics, genetic associations with any postsecondary education and college completion were moderated by school-level socioeconomic status. Along similar lines, we observe substantial between-school variation in the average level of educational attainment students achieved for a fixed genotype. These findings emphasize the importance of social context in the interpretation of genetic associations. Specifically, our results suggest that though existing measures of individual genetic endowment have a linear relationship with years of schooling that is relatively consistent across school environments, school context is crucial in connecting an individual's genotype to his or her likelihood of crossing meaningful educational thresholds.

Your Face is Your Fortune: Does Adolescent Attractiveness Predict Intimate Relationships Later in Life?

OBJECTIVE: A growing literature documents the importance of physical attractiveness in young and middle adulthood for romantic, marital, and sexual relationships, but little is known about how attractiveness in adolescence matters to intimate relationships in later life. We ask: does attractiveness early in life convey ongoing benefits late in life, or do such benefits erode over time? METHODS: We use multivariate regression models and more than 50 years of data from the Wisconsin Longitudinal Study to examine the connections between adolescent physical attractiveness and intimate relationships (i.e., sexual activity and access to potential sexual partners) in later life. RESULTS: We find that adolescent attractiveness facilitates sexual activity in later life. This relationship is largely driven by attractiveness increasing the probability of having access to potential sexual partners. However, attractiveness is not related to sexual activity among married couples, even after controlling for marital duration. Men, those in good health, and wealthier individuals are also more likely to engage in several facets of intimate relationships. DISCUSSION: These findings highlight the importance of relationship context for later life sexual activity and begin to explicate the pathways through which factors across the life course-particularly attractiveness-influence sexual activity in later life.

Human longevity: 25 genetic loci associated in 389,166 UK biobank participants.

We undertook a genome-wide association study (GWAS) of parental longevity in European descent UK Biobank participants. For combined mothers' and fathers' attained age, 10 loci were associated (p<5*10-8), including 8 previously identified for traits including survival, Alzheimer's and cardiovascular disease. Of these, 4 were also associated with longest 10% survival (mothers age ≥90 years, fathers ≥87 years), with 2 additional associations including MC2R intronic variants (coding for the adrenocorticotropic hormone receptor). Mother's age at death was associated with 3 additional loci (2 linked to autoimmune conditions), and 8 for fathers only. An attained age genetic risk score associated with parental survival in the US Health and Retirement Study and the Wisconsin Longitudinal Study and with having a centenarian parent (n=1,181) in UK Biobank. The results suggest that human longevity is highly polygenic with prominent roles for loci likely involved in cellular senescence and inflammation, plus lipid metabolism and cardiovascular conditions. There may also be gender specific routes to longevity.

FACIAL ATTRACTIVENESS AND LIFETIME EARNINGS: EVIDENCE FROM A COHORT STUDY.

We use unique longitudinal data to document an economically and statistically significant positive correlation between the facial attractiveness of male high school graduates and their subsequent labor market earnings. There are only weak links between facial attractiveness and direct measures of cognitive skills and no link between facial attractiveness and mortality. Even after including a lengthy set of characteristics, including IQ, high school activities, proxy measures for confidence and personality, family background, and additional respondent characteristics in an empirical model of earnings, the attractiveness premium is present in the respondents' mid-30s and early 50s. Our findings are consistent with attractiveness being an enduring, positive labor market characteristic.