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Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. Education is strongly genetically correlated with intelligence (rg = 0.70). We used these findings as foundations for our use of a novel approach—multi-trait analysis of genome-wide association studies (MTAG; Turley et al. 2017)—to combine two large genome-wide association studies (GWASs) of education and intelligence, increasing statistical power and resulting in the largest GWAS of intelligence yet reported. Our study had four goals: first, to facilitate the discovery of new genetic loci associated with intelligence; second, to add to our understanding of the biology of intelligence differences; third, to examine whether combining genetically correlated traits in this way produces results consistent with the primary phenotype of intelligence; and, finally, to test how well this new meta-analytic data sample on intelligence predicts phenotypic intelligence in an independent sample. By combining datasets using MTAG, our functional sample size increased from 199,242 participants to 248,482. We found 187 independent loci associated with intelligence, implicating 538 genes, using both SNP-based and gene-based GWAS. We found evidence that neurogenesis and myelination—as well as genes expressed in the synapse, and those involved in the regulation of the nervous system—may explain some of the biological differences in intelligence. The results of our combined analysis demonstrated the same pattern of genetic correlations as those from previous GWASs of intelligence, providing support for the meta-analysis of these genetically-related phenotypes.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Background While the associations between personality traits and self-reported physical activity are well replicated, few studies have examined the associations between personality and device-based measures of both physical activity and sedentary behaviour. Low levels of physical activity and high levels of sedentary behaviour are known risk factors for poorer health outcomes in older age. Methods We used device-based measures of physical activity and sedentary behaviour recorded over 7 days in 271 79-year-old participants of the Lothian Birth Cohort 1936. Linear regression models were used to assess whether personality traits were cross-sectionally associated with step count, sedentary time, and the number of sit-to-stand transitions. Personality traits were entered one at a time, and all-together, controlling for age and sex in Model 1 and additionally for BMI and limiting long-term illness in Model 2. Results None of the associations between personality traits and measures of physical activity and sedentary behaviours remained significant after controlling for multiple-comparisons using the False Discovery Rate test (all ps > .07). Conclusions We found no evidence that personality traits are associated with device-based measures of physical activity or sedentary behaviour in older age. More studies are needed to replicate and examine the nature of these relationships.

Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n =53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissuespecific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ∼2.6% of the SNPs from each GWAS but accounted for ∼ 40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions.

People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108 038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (β between 0.009–0.043), and in a negative direction in the case of body mass index (β=−0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.

People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108 038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (β between 0.009–0.043), and in a negative direction in the case of body mass index (β=−0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.

Background: The English NHS Bowel Cancer Screening Programme has offered biennial faecal occult blood testing to people aged 60–69?years since 2006, and to those aged 60–74?years since 2010. Analysis of the first 2.6 million screening invitations found that 54% of eligible people took up the invitation. The reasons for this low uptake are unclear. We investigated whether participation in screening varies according to cognitive ability and personality.Methods: Participants were members of The English Longitudinal Study of Ageing. In 2010–2011, respondents were asked about participation in bowel cancer screening, and cognitive ability and the ‘Big Five’ personality traits were assessed. Logistic regression was used to examine the cross-sectional relationships between cognitive ability and personality and screening participation in 2681 people aged 60–75?years who were eligible to have been invited to take part in the UK national screening programme for bowel cancer.Results: In age-adjusted and sex-adjusted analyses, better cognition and higher conscientiousness were associated with increased participation in cancer screening. ORs (95% CIs) per SD increase were 1.10 (1.03 to 1.18) for cognitive ability and 1.10 (1.01 to 1.19) for conscientiousness. After further adjustment for household wealth and health literacy—shown previously to be associated with participation—these associations were attenuated (ORs were 1.07 (1.00 to 1.15) and 1.07 (0.97 to 1.18), respectively).Conclusions: We found some indication that better cognitive function and greater conscientiousness may be linked with a slightly increased likelihood of participation in bowel cancer screening. These relationships need investigation in other cohorts of older people.

Background\ud \ud \ud Differences between the arms in systolic blood pressure (SBP) of ≥10 mmHg have been associated with an increased risk of mortality in patients with hypertensive and chronic renal disease. For the first time, we examined these relationships in a non-clinical population.\ud \ud \ud \ud Design\ud \ud \ud Cohort study.\ud \ud \ud \ud Methods\ud \ud \ud Participants were 4419 men (mean age 38.37 years) from the Vietnam Experience Study. Bilateral SBP and diastolic BP (DBP), serum lipids, fasting glucose, erythrocyte sedimentation rate, metabolic syndrome, and ankle brachial index were assessed in 1986.\ud \ud \ud \ud Results\ud \ud \ud Ten per cent of men had an interarm difference of ≥10 and 2.4% of ≥15 mmHg. A 15-year follow-up period gave rise to 246 deaths (64 from cardiovascular disease, CVD). Interarm differences of ≥10 mmHg were associated with an elevated risk of all-cause mortality (hazard ratio, HR, 1.49, 95% confidence interval, CI, 1.04–2.14) and CVD mortality (HR 1.93, 95% CI 1.01–3.69). After adjusting for SBP, DBP, lipids, fasting glucose, and erythrocyte sedimentation rate, associations between interarm differences of ≥10 mmHg and all-cause mortality (HR 1.35, 95% CI 0.94–1.95) and CVD mortality (1.62, 95% CI 0.84–3.14) were significantly attenuated.\ud \ud \ud \ud Conclusions\ud \ud \ud In this non-clinical cohort study, interarm differences in SBP were not associated with mortality after accounting for traditional CVD risk factors. Interarm differences might not be valuable as an additional risk factor for mortality in populations with a low risk of CVD.

OBJECTIVES--To determine whether vitamin C status, as measured by dietary intake and plasma ascorbic acid concentration, is related to mortality from stroke and coronary heart disease in people aged 65 and over. DESIGN--A 20 year follow up study of a cohort of randomly selected elderly people living in the community who had taken part in the 1973-4 Department of Health and Social Security nutritional survey and for whom dietary and other data had been recorded. SETTING--Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS--730 men and women who had completed a seven day dietary record and who had no history or symptoms of stroke, cerebral arteriosclerosis, or coronary heart disease when examined by a geriatrician in 1973-4. RESULTS--Mortality from stroke was highest in those with the lowest vitamin C status. Those in the highest third of the distribution of vitamin C intake had a relative risk of 0.5 (95% confidence interval 0.3 to 0.8) compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors. The relation between vitamin C intake and stroke was independent of social class and other dietary variables. A similar gradient in risk was present for plasma ascorbic acid concentrations. No association was found between vitamin C status and risk of death from coronary heart disease. CONCLUSION--In elderly people vitamin C concentration, whether measured by dietary intake or plasma concentration of ascorbic acid, is strongly related to subsequent risk of death from stroke but not from coronary heart disease.