Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)
; heritability estimated from twin studies ranges from 30 to 50%
, and ...SNP-based heritability ranges from 6 to 15%
. Increased neuroticism is associated with poorer mental and physical health
, translating to high economic burden
. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci
. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (r
= 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; r
= 0.69, s.e. = 0.07) and subjective well-being (r
= -0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.
Pedigree-based analyses of intelligence have reported that genetic differences account for 50-80% of the phenotypic variation. For personality traits these effects are smaller, with 34-48% of the ...variance being explained by genetic differences. However, molecular genetic studies using unrelated individuals typically report a heritability estimate of around 30% for intelligence and between 0 and 15% for personality variables. Pedigree-based estimates and molecular genetic estimates may differ because current genotyping platforms are poor at tagging causal variants, variants with low minor allele frequency, copy number variants, and structural variants. Using ~20,000 individuals in the Generation Scotland family cohort genotyped for ~700,000 single-nucleotide polymorphisms (SNPs), we exploit the high levels of linkage disequilibrium (LD) found in members of the same family to quantify the total effect of genetic variants that are not tagged in GWAS of unrelated individuals. In our models, genetic variants in low LD with genotyped SNPs explain over half of the genetic variance in intelligence, education, and neuroticism. By capturing these additional genetic effects our models closely approximate the heritability estimates from twin studies for intelligence and education, but not for neuroticism and extraversion. We then replicated our finding using imputed molecular genetic data from unrelated individuals to show that ~50% of differences in intelligence, and ~40% of the differences in education, can be explained by genetic effects when a larger number of rare SNPs are included. From an evolutionary genetic perspective, a substantial contribution of rare genetic variants to individual differences in intelligence, and education is consistent with mutation-selection balance.
Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are ...estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.
Visual acuity significantly contributes to quality of life. Deficits in childhood are associated with reading difficulties, which can have detrimental effects on education outcomes. In adults, it has ...been observed that vision defects such as myopia are associated with higher educational attainment (EA). Understanding genetic factors contributing to visual acuity could help to dissect its links with cognitive skills, neurodevelopmental conditions, and education. We examined associations between distance visual acuity, cognitive measures including school grades, and neurodevelopmental conditions in a longitudinal cohort of British children (ALSPAC, n = 6807, M age = 11.8). We performed a genome-wide association study (GWAS, n = 5571) on visual acuity and tested for genetic associations with relevant phenotypes using polygenic scores (PGS) and genetic correlation analyses. Visual acuity was associated with better cognitive performance and school grades, and reduced in individuals with reading difficulties compared to controls. GWAS revealed genetic associations at the NPLOC4 locus and highlighted other genes involved in sensory function. In line with positive genetic correlations between visual acuity and cognitive measures, EA PGS were positively associated with visual acuity, while there was a less robust negative association with myopia PGS. In conclusion, increased visual acuity is associated with a range of positive outcomes, including better school grades. Our results suggest an association between a higher EA PGS and slightly increased visual acuity in childhood. This could indicate gene-environment correlation, in which environmental exposures linked to higher EA might have detrimental effects on vision offsetting the initial positive effect.
Purpose: Reading and speech difficulties are common in childhood, yet it is not fully understood how much of their etiology is shared. This partly derives from methodological issues related to ...overlooking the potential co-occurrence between the two sets of difficulties. This study investigated the effects of five bioenvironmental predictors in a sample assessed for such co-occurrence. Method: A combination of exploratory and confirmatory analyses was performed on longitudinal data from the National Child Development Study. Exploratory latent class analysis was performed on children's reading, speech, and language outcomes at ages 7 and 11 years. Membership in the obtained classes was modeled using a regression with sex and four early-life predictors: gestation period, socioeconomic status, maternal education, and the home reading environment. Results: The model yielded four latent classes that broadly reflected (1) average reading and speech, (2) excellent reading, (3) reading difficulties, and (4) speech difficulties. Early-life factors significantly predicted class membership. Male sex and preterm birth emerged as risk factors for both reading and speech difficulties. Protective effects against reading difficulties were identified for maternal education, and lower (but not higher) levels of socioeconomic status and the home reading environment. Conclusions: Co-occurrence of reading and speech difficulties in the sample was low, and differential patterns of effect of the social environment were supported. Reading outcomes were under stronger malleable influence than speech outcomes.
It is suggested that the brain's peak width of skeletonized water mean diffusivity (PSMD) is a neuro-biomarker of processing speed, an important aspect of cognitive aging. We tested whether PSMD is ...more strongly correlated with processing speed than with other cognitive domains, and more strongly than other structural brain MRI indices. Participants were 731 Lothian Birth Cohort 1936 members, mean age = 73 years (SD = 0.7); analytical sample was 656-680. Cognitive domains tested were as follows: processing speed (5 tests), visuospatial (3), memory (3), and verbal (3). Brain-imaging variables included PSMD, white matter diffusion parameters, hyperintensity volumes, gray and white matter volumes, and perivascular spaces. PSMD was significantly associated with processing speed (-0.27), visuospatial ability (-0.23), memory ability (-0.17), and general cognitive ability (-0.25); comparable correlations were found with other brain-imaging measures. In a multivariable model with the other imaging variables, PSMD provided independent prediction of visuospatial ability and general cognitive ability. This incremental prediction, coupled with its ease to compute and possibly better tractability, might make PSMD a useful brain biomarker in studies of cognitive aging.
Subjective wellbeing (SWB) has been widely accepted as one of the most important elements of successful ageing. The present study explores the impact of two well-established correlates of SWB: ...physical activity and personality. Physical activity and each of the Big Five personality traits are consistent predictors of SWB, but there has been little research on whether certain personality traits enhance or hinder the psychological benefits of physical activity in older adults. This study examines the interactions of leisure-time physical activity and personality traits on SWB, and whether such interactions vary between older adults in Hong Kong (HK) and older adults in the United Kingdom (UK). Altogether, 349 participants (178 HK, 171 UK; 157 males, 192 female) aged 50 years or above (mean age = 61.84 ± 8.46 years old) completed an online assessment of: (1) leisure-time physical activity (Godin⁻Shephard Leisure-Time Physical Activity Questionnaire); (2) personality traits (Big Five Inventory); and (3) SWB (Satisfaction with Life Scale, Positive and Negative Affect Schedule). Results showed that agreeableness, conscientiousness, extraversion, neuroticism, openness to experience, and physical activity were all significantly related to SWB in the expected direction. The relationship between physical activity and SWB was moderated by extraversion and by openness to experience: higher levels of these two traits significantly enhanced the relationship. None of the interactions varied between the HK and UK samples. The expected negative relationship between neuroticism and SWB, however, was significantly stronger in the UK sample than in the HK sample. The findings of the present study indicate that personality needs to be considered when promoting and providing physical activity for older adults, although more research is needed to further explore how this can work effectively.
eCFM is an extension of context-aware feature modeling (CFM) that improves contextual variability's expressiveness. eCFM combined with model checking provides a systematic way to model dynamically ...adaptable software and avoid failures in it.
•Motoric Cognitive Risk (MCR) syndrome is a high-risk state for adverse health outcomes in older adults characterised by measured slow gait speed and self-reported cognitive complaints.•We used both ...Cox proportional hazards and competing risk regression methods to evaluate the risk of developing all-cause incident dementia over 10 years of follow-up for individuals with and without MCR.•The presence of MCR increased the risk of incident dementia (adjusted hazard ratio 2.34, 95%CI 1.14-4.78, p=0.020), as did fewer years of education and higher depression symptoms.•MCR showed similar prognostic ability for dementia in a Scottish cohort as for other populations. MCR could identify a target group for early interventions of modifiable risk factors to prevent incident dementia.
Motoric Cognitive Risk (MCR) syndrome is a high-risk state for adverse health outcomes in older adults characterised by measured slow gait speed and self-reported cognitive complaints. The recent addition to the Lothian Birth Cohort 1936 of robust dementia outcomes enabled us to assess the prognostic value of MCR for dementia and explore the various trajectories of participants diagnosed with MCR.
We classified 680 community-dwelling participants free from dementia into non-MCR or MCR groups at mean SD age 76.3 0.8 years. We used Cox and competing risk regression methods, adjusted for potential confounders, to evaluate the risk of developing all-cause incident dementia over 10 years of follow-up. Secondarily, we followed the trajectories for individuals with and without MCR at baseline and categorised them into subgroups based on whether MCR was still present at the next research wave, three years later.
The presence of MCR increased the risk of incident dementia (adjusted HR 2.34, 95%CI 1.14-4.78, p=0.020), as did fewer years of education and higher depression symptoms. However, MCR has a heterogenous progression trajectory. The MCR progression subgroups each have different prognostic values for incident dementia.
MCR showed similar prognostic ability for dementia in a Scottish cohort as for other populations. MCR could identify a target group for early interventions of modifiable risk factors to prevent incident dementia. This study illustrates the heterogeneous nature of MCR progression. Exploring the underlying reasons will be important work in future work.
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