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Objective: Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, that is, the frailty index, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and longitudinally, and to investigate the contribution of shared genetic influences., Methods: Data were derived from the UK Biobank (UKB; n = 274,951), the Australian Over 50's Study (AO50; n = 2849), and the Swedish Twin Registry (Screening Across the Lifespan of Twins Study [SALT], n = 18,960; The Swedish Adoption/Twin Study of Aging [SATSA], n = 1365). Associations between neuroticism and the frailty index were investigated using regression analysis cross-sectionally in UKB, AO50, and SATSA and longitudinally in SALT (25-29 years of follow-up) and SATSA (6 and 23 years of follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism were used in all samples to further assess whether common genetic variants associated with neuroticism predict frailty., Results: High neuroticism was consistently associated with greater frailty cross-sectionally (adjusted β [95% confidence intervals] in UKB = 0.32 [0.32-0.33]; AO50 = 0.35 [0.31-0.39]; SATSA = 0.33 [0.27-0.39]) and longitudinally up to 29 years (SALT = 0.24 [0.22-0.25]; SATSA 6 years = 0.31 [0.24-0.38]; SATSA 23 years = 0.16 [0.07-0.25]). When adjusting for underlying shared genetic and environmental factors, the neuroticism-frailty association remained significant, although decreased. Polygenic risk scores for neuroticism significantly predicted frailty in the two larger samples (meta-analyzed total β = 0.059 [0.055-0.062])., Conclusions: Neuroticism in midlife predicts frailty in late life. Neuroticism may have a causal influence on frailty, whereas both environmental and genetic influences, including neuroticism-associated common genetic variants, contribute to this relationship.

"Executive functions" (EF) is a multidimensional construct which encompasses many higher-order cognitive control operations, and is considered a potential mediator of age-associated changes in other cognitive domains. Here we examine the heritability of four measures of EF, and the genetic influences on their covariation with general cognitive abilities (GCA) from the Older Australian Twins Study. Participants included 117 pairs of monozygotic twins, 98 pairs of dizygotic twins, and 42 single twins, with a mean age of 71. Genetic modeling showed that additive genetic factors contributed to 59, 63,29, and 31% of the variance in the four measures: working memory, verbal fluency, response inhibition and cognitive flexibility, respectively. The phenotypic associations among the four EF measures were modest, which is in line with other evidence that EF is a multi-dimensional construct.All of the covariation between the EF measures was attributable to a common genetic factor. Similarly, all of the covariation between EF and General Cognitive Ability was explained by a common genetic factor, with no significant covariance due to environmental (E) factors. The genetic correlations between the measures were moderately high, suggesting that they may have common biological underpinnings. The genetic influence in the covariation of the EF measures and GCA also suggests that some aspects of EF and GCA share the same genes or same set of genes.

Optimism has been shown to be important in maintaining wellbeing into old age, but little is known about the sources of variation in optimism and its links to mental and somatic health. Optimism, mental, and self-rated health were measured in 3,053 twin individuals (501 MZF, 153 MZM, 274 DZF, 77 DZM, and 242 DZ opposite-sex twin pairs and 561 single twins) over 50 years using the life orientation test, the General Health Questionnaire and a single-item question for self-rated health. Additive genetic factors explained 36, 34, and 46% of the variation in optimism, mental, and self-rated health, respectively, with the remainder being due to non-shared environmental influences. Genetic influences accounted for most of the covariance between the variables (14-20% of the genetic variance) indicating that in older adults genes predisposing to high optimism also predispose to good mental health and self-rated health.

Objectives The educational gradient in late-life health is well established. Despite this, there are still ambiguities concerning the role of underlying confounding by genetic influences and gene-environment (GE) interplay. Here, we investigate the role of educational factors (attained and genetic propensities) on health and mortality in late life using genetic propensity for educational attainment (as measured by a genome-wide polygenic score, PGSEdu) and attained education. Methods By utilizing genetically informative twin data from the Swedish Twin Registry (n = 14,570), we investigated influences of the educational measures, familial confounding as well as the possible presence of passive GE correlation on both objective and subjective indicators of late-life health, that is, the Frailty Index, Multimorbidity, Self-rated health, cardiovascular disease, and all-cause mortality. Results Using between-within models to adjust for shared familial factors, we found that the relationship between educational level and health and mortality later in life persisted despite controlling for familial confounding. PGSEdu and attained education both uniquely predicted late-life health and mortality, even when mutually adjusted. Between-within models of PGSEdu on the health outcomes in dizygotic twins showed weak evidence for passive GE correlation (prGE) in the education-health relationship. Discussion Both genetic propensity to education and attained education are (partly) independently associated with health in late life. These results lend further support for a causal education-health relationship but also raise the importance of genetic contributions and GE interplay. [ABSTRACT FROM AUTHOR]