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1.
Arterioscler Thromb Vasc Biol ; : ATVBAHA119312552, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597446

RESUMO

OBJECTIVE: The retina may provide readily accessible imaging biomarkers of global cardiovascular health. Increasing evidence suggests variation in retinal vascular traits is highly heritable. This study aimed to identify the genetic determinants of retinal vascular traits. Approach and Results: We conducted a meta-analysis of genome-wide association studies for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside; N=1736) and ORCADES (Orkney Complex Disease Study; N=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 (ACTN4/CAPN12) for retinal venular tortuosity (TortV), and one at 13q34 (COL4A2) for retinal arteriolar tortuosity (TortA); these 2 loci were subsequently confirmed in 3 independent cohorts (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (ßs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (ßs.d.=0.103; SE=0.015; P=4.66×10-12). Notably, the ACTN4/CAPN12 locus associated with TortV is also associated with coronary artery disease, heart rate, and atrial fibrillation. CONCLUSIONS: Genetic determinants of retinal vascular tortuosity are also linked to cardiovascular health. These findings provide a molecular pathophysiological foundation for the use of retinal vascular traits as biomarkers for cardiovascular diseases.

2.
Transl Psychiatry ; 9(1): 248, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591380

RESUMO

Recent advances in genome-wide DNA methylation (DNAm) profiling for smoking behaviour have given rise to a new, molecular biomarker of smoking exposure. It is unclear whether a smoking-associated DNAm (epigenetic) score has predictive value for ageing-related health outcomes which is independent of contributions from self-reported (phenotypic) smoking measures. Blood DNA methylation levels were measured in 895 adults aged 70 years in the Lothian Birth Cohort 1936 (LBC1936) study using the Illumina 450K assay. A DNA methylation score based on 230 CpGs was used as a proxy for smoking exposure. Associations between smoking variables and health outcomes at age 70 were modelled using general linear modelling (ANCOVA) and logistic regression. Additional analyses of smoking with brain MRI measures at age 73 (n = 532) were performed. Smoking-DNAm scores were positively associated with self-reported smoking status (P < 0.001, eta-squared ɳ2 = 0.63) and smoking pack years (r = 0.69, P < 0.001). Higher smoking DNAm scores were associated with variables related to poorer cognitive function, structural brain integrity, physical health, and psychosocial health. Compared with phenotypic smoking, the methylation marker provided stronger associations with all of the cognitive function scores, especially visuospatial ability (P < 0.001, partial eta-squared ɳp2 = 0.022) and processing speed (P < 0.001, ɳp2 = 0.030); inflammatory markers (all P < 0.001, ranges from ɳp2 = 0.021 to 0.030); dietary patterns (healthy diet (P < 0.001, ɳp2 = 0.052) and traditional diet (P < 0.001, ɳp2 = 0.032); stroke (P = 0.006, OR 1.48, 95% CI 1.12, 1.96); mortality (P < 0.001, OR 1.59, 95% CI 1.42, 1.79), and at age 73; with MRI volumetric measures (all P < 0.001, ranges from ɳp2 = 0.030 to 0.052). Additionally, education was the most important life-course predictor of lifetime smoking tested. Our results suggest that a smoking-associated methylation biomarker typically explains a greater proportion of the variance in some smoking-related morbidities in older adults, than phenotypic measures of smoking exposure, with some of the accounted-for variance being independent of phenotypic smoking status.

3.
Psychol Med ; : 1-10, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31576797

RESUMO

BACKGROUND: Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. METHODS: We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu. RESULTS: We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education. CONCLUSION: Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.

4.
Epigenomics ; 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31536415

RESUMO

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

5.
Elife ; 82019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31526476

RESUMO

Intelligence and education are predictive of better physical and mental health, socioeconomic position (SEP), and longevity. However, these associations are insufficient to prove that intelligence and/or education cause these outcomes. Intelligence and education are phenotypically and genetically correlated, which makes it difficult to elucidate causal relationships. We used univariate and multivariable Mendelian randomization to estimate the total and direct effects of intelligence and educational attainment on mental and physical health, measures of socioeconomic position, and longevity. Both intelligence and education had beneficial total effects. Higher intelligence had positive direct effects on income and alcohol consumption, and negative direct effects on moderate and vigorous physical activity. Higher educational attainment had positive direct effects on income, alcohol consumption, and vigorous physical activity, and negative direct effects on smoking, BMI and sedentary behaviour. If the Mendelian randomization assumptions hold, these findings suggest that both intelligence and education affect health.

6.
Curr Biol ; 29(16): R786-R787, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430471

RESUMO

Age-related clonal haemopoiesis (ARCH) in healthy individuals was initially observed through an increased skewing in X-chromosome inactivation [1]. More recently, several groups reported that ARCH is driven by somatic mutations [2], with the most prevalent ARCH mutations being in the DNMT3A and TET2 genes, previously described as drivers of myeloid malignancies. ARCH is associated with an increased risk for haematological cancers [2]. ARCH also confers an increased risk for non-haematological diseases, such as cardiovascular disease, atherosclerosis, and chronic ischemic heart failure, for which age is a main risk factor [3,4]. Whether ARCH is linked to accelerated ageing has remained unexplored. The most accurate and commonly used tools to measure age acceleration are epigenetic clocks: they are based on age-related methylation differences at specific CpG sites [5]. Deviations from chronological age towards an increased epigenetic age have been associated with increased risk of earlier mortality and age-related morbidities [5,6]. Here we present evidence of accelerated epigenetic age in individuals with ARCH.

7.
Br J Psychiatry ; : 1-8, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412972

RESUMO

BACKGROUND: Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear. AIMS: To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors. METHOD: Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation. RESULTS: Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range -0.23 to -0.17 (95% CI -0.39 to -0.03) across different estimation methods, and for the major depression group they were approximately -0.07 (95% CI -0.10 to -0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (-0.05; 95% CI -0.09 to -0.01). No evidence was found for mediation via cardiometabolic disease. CONCLUSIONS: In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow. DECLARATION OF INTEREST: I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee.

8.
Aging (Albany NY) ; 11(16): 5895-5923, 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31422385

RESUMO

Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p=3.5E-6), and iv) association with smoking history (p=1.21E-17). These associations are further validated in large scale methylation data (n=10k samples) from the Framingham Heart Study, Women's Health Initiative, Jackson Heart Study, InChianti, Lothian Birth Cohorts, Twins UK, and Bogalusa Heart Study. Leukocyte DNAmTL is also associated with measures of physical fitness/functioning (p=0.029), age-at-menopause (p=0.039), dietary variables (omega 3, fish, vegetable intake), educational attainment (p=3.3E-8) and income (p=3.1E-5). Experiments in cultured somatic cells show that DNAmTL dynamics reflect in part cell replication rather than TL per se. DNAmTL is not only an epigenetic biomarker of replicative history of cells, but a useful marker of age-related pathologies that are associated with it.

9.
Genome Med ; 11(1): 54, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443728

RESUMO

BACKGROUND: DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed 'epigenetic clocks'. The deviation of predicted age from the actual age ('age acceleration residual', AAR) has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affects such association. METHODS: In this study, we build multiple predictors based on training DNA methylation samples selected from 13,661 samples (13,402 from blood and 259 from saliva). We use the Lothian Birth Cohorts of 1921 (LBC1921) and 1936 (LBC1936) to examine whether the association between AAR (from these predictors) and death is affected by (1) improving prediction accuracy of an age predictor as its training sample size increases (from 335 to 12,710) and (2) additionally correcting for confounders (i.e., cellular compositions). In addition, we investigated the performance of our predictor in non-blood tissues. RESULTS: We found that in principle, a near-perfect age predictor could be developed when the training sample size is sufficiently large. The association between AAR and mortality attenuates as prediction accuracy increases. AAR from our best predictor (based on Elastic Net, https://github.com/qzhang314/DNAm-based-age-predictor ) exhibits no association with mortality in both LBC1921 (hazard ratio = 1.08, 95% CI 0.91-1.27) and LBC1936 (hazard ratio = 1.00, 95% CI 0.79-1.28). Predictors based on small sample size are prone to confounding by cellular compositions relative to those from large sample size. We observed comparable performance of our predictor in non-blood tissues with a multi-tissue-based predictor. CONCLUSIONS: This study indicates that the epigenetic clock can be improved by increasing the training sample size and that its association with mortality attenuates with increased prediction of chronological age.

10.
Aging (Albany NY) ; 11(16): 5876-5894, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31461406

RESUMO

Telomere length is associated with age-related diseases and is highly heritable. It is unclear, however, to what extent epigenetic modifications are associated with leukocyte telomere length (LTL). In this study, we conducted a large-scale epigenome-wide association study (EWAS) of LTL using seven large cohorts (n=5,713) - the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins. Our stratified analysis suggests that EWAS findings for women of African ancestry may be distinct from those of three other groups: males of African ancestry, and males and females of European ancestry. Using a meta-analysis framework, we identified DNA methylation (DNAm) levels at 823 CpG sites to be significantly associated (P<1E-7) with LTL after adjusting for age, sex, ethnicity, and imputed white blood cell counts. Functional enrichment analyses revealed that these CpG sites are near genes that play a role in circadian rhythm, blood coagulation, and wound healing. Weighted correlation network analysis identified four co-methylation modules associated with LTL, age, and blood cell counts. Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes.

11.
Psychol Aging ; 34(6): 766-779, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31393145

RESUMO

Hearing impairment is associated with poorer cognitive function in later life. We tested for the potential contribution of childhood cognitive ability to this relationship. Childhood cognitive ability is strongly related to cognitive function in older age, and may be related to auditory function through its association with hearing impairment risk factors. Using data from the Lothian Birth Cohort, 1936, we tested whether childhood cognitive ability predicted later-life hearing ability then whether this association was mediated by demographic or health differences. We found that childhood cognitive ability was negatively associated with hearing impairment risk at age 76 (odds ratio = .834, p = .042). However, this association was nonsignificant after subsequent adjustment for potentially mediating demographic and health factors. Next, we tested whether associations observed in older age between hearing impairment and general cognitive ability level or change were accounted for by childhood cognitive ability. At age 76, in the minimally adjusted model, hearing impairment was associated with poorer general cognitive ability level (ß = -.119, p = .030) but was not related to decline in general cognitive ability. The former association became nonsignificant after additional adjustment for childhood cognitive ability (ß = -.068, p = .426) suggesting that childhood cognitive ability contributes (potentially via demographic and health differences) to the association between levels of hearing and cognitive function in older age. Further work is needed to test whether early life cognitive ability also contributes to the association (documented in previous studies) between older-age hearing impairment and cognitive decline. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

12.
Int J Epidemiol ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263887

RESUMO

BACKGROUND: People who opt to participate in scientific studies tend to be healthier, wealthier and more educated than the broader population. Although selection bias does not always pose a problem for analysing the relationships between exposures and diseases or other outcomes, it can lead to biased effect size estimates. Biased estimates may weaken the utility of genetic findings because the goal is often to make inferences in a new sample (such as in polygenic risk score analysis). METHODS: We used data from UK Biobank, Generation Scotland and Partners Biobank and conducted phenotypic and genome-wide association analyses on two phenotypes that reflected mental health data availability: (i) whether participants were contactable by e-mail for follow-up; and (ii) whether participants responded to follow-up surveys of mental health. RESULTS: In UK Biobank, we identified nine genetic loci associated (P <5 × 10-8) with e-mail contact and 25 loci associated with mental health survey completion. Both phenotypes were positively genetically correlated with higher educational attainment and better health and negatively genetically correlated with psychological distress and schizophrenia. One single nucleotide polymorphism association replicated along with the overall direction of effect of all association results. CONCLUSIONS: Re-contact availability and follow-up participation can act as further genetic filters for data on mental health phenotypes.

13.
Psychol Med ; : 1-10, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31317844

RESUMO

BACKGROUND: Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ. METHODS: The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants. RESULTS: There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (ß = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (ß = 0.098, p = 0.026), compared to a negative association among controls (ß = -0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons. CONCLUSIONS: Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.

14.
Nat Commun ; 10(1): 3160, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320639

RESUMO

Although plasma proteins may serve as markers of neurological disease risk, the molecular mechanisms responsible for inter-individual variation in plasma protein levels are poorly understood. Therefore, we conduct genome- and epigenome-wide association studies on the levels of 92 neurological proteins to identify genetic and epigenetic loci associated with their plasma concentrations (n = 750 healthy older adults). We identify 41 independent genome-wide significant (P < 5.4 × 10-10) loci for 33 proteins and 26 epigenome-wide significant (P < 3.9 × 10-10) sites associated with the levels of 9 proteins. Using this information, we identify biological pathways in which putative neurological biomarkers are implicated (neurological, immunological and extracellular matrix metabolic pathways). We also observe causal relationships (by Mendelian randomisation analysis) between changes in gene expression (DRAXIN, MDGA1 and KYNU), or DNA methylation profiles (MATN3, MDGA1 and NEP), and altered plasma protein levels. Together, this may help inform causal relationships between biomarkers and neurological diseases.

15.
Biol Psychiatry ; 86(7): 536-544, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171358

RESUMO

BACKGROUND: Schizophrenia is a neurodevelopmental disorder with many genetic variants of individually small effect contributing to phenotypic variation. Lower cortical thickness (CT), surface area, and cortical volume have been demonstrated in people with schizophrenia. Furthermore, a range of obstetric complications (e.g., lower birth weight) are consistently associated with an increased risk for schizophrenia. We investigated whether a high polygenic risk score for schizophrenia (PGRS-SCZ) is associated with CT, surface area, and cortical volume in UK Biobank, a population-based sample, and tested for interactions with birth weight. METHODS: Data were available for 2864 participants (nmale/nfemale = 1382/1482; mean age = 62.35 years, SD = 7.40). Linear mixed models were used to test for associations among PGRS-SCZ and cortical volume, surface area, and CT and between PGRS-SCZ and birth weight. Interaction effects of these variables on cortical structure were also tested. RESULTS: We found a significant negative association between PGRS-SCZ and global CT; a higher PGRS-SCZ was associated with lower CT across the whole brain. We also report a significant negative association between PGRS-SCZ and insular lobe CT. PGRS-SCZ was not associated with birth weight and no PGRS-SCZ × birth weight interactions were found. CONCLUSIONS: These results suggest that individual differences in CT are partly influenced by genetic variants and are most likely not due to factors downstream of disease onset. This approach may help to elucidate the genetic pathophysiology of schizophrenia. Further investigation in case-control and high-risk samples could help identify any localized effects of PGRS-SCZ, and other potential schizophrenia risk factors, on CT as symptoms develop.

16.
17.
J Epidemiol Community Health ; 73(8): 712-716, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152074

RESUMO

BACKGROUND: Studies with single baseline measurements of cognitive function consistently reveal inverse relationships with mortality risk. The relation of change in functioning, particularly from early in the life course, which may offer additional insights into causality, has not, to the best of our knowledge, been tested. AIMS: To examine the association of change in cognition between late adolescence and middle age with cause-specific mortality using data from a prospective cohort study. METHODS: The analytical sample consisted of 4289 former US male military personnel who were administered the Army General Technical Test in early adulthood (mean age 20.4 years) and again in middle age (mean age 38.3 years). RESULTS: A 15-year period of mortality surveillance subsequent to the second phase of cognitive testing gave rise to 237 deaths. Following adjustment for age, a 10-unit increase in cognitive function was related to a reduced risk of death from all causes (HR 0.84; 95% CI 0.75 to 0.93) and cardiovascular disease (HR 0.78; 95% CI 0.64 to 0.95) but not from all cancers (HR 1.14; 95% CI 0.88 to 1.47) nor injury (HR 1.02; 95% CI 0.81 to 1.29). Adjustment for markers of socioeconomic status in middle age resulted in marked attenuation in the magnitude of these associations and statistical significance at conventional levels was lost in all analyses. CONCLUSIONS: In the present study, the apparent link between increased cognition and mortality was mediated by socioeconomic status.

18.
Cereb Cortex ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240317

RESUMO

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.

19.
Neuropsychology ; 33(5): 642-657, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246073

RESUMO

OBJECTIVE: Mean speed of responding is the most commonly used measure in the assessment of reaction time (RT). An alternative measure is intraindividual variability (IIV): the inconsistency of responding across multiple trials of a test. IIV has been suggested as an important indicator of central nervous system functioning, and as such, there has been increasing interest in the associations between IIV and brain imaging metrics. Results however, have been inconsistent. The present seeks to provide a comprehensive evaluation of the associations between a variety of measures of brain white matter integrity and individual differences in choice RT (CRT) IIV. METHOD: MRI brain scans of members of the Lothian Birth Cohort 1936 were assessed to obtain measures of the volume and severity of white matter hyperintensities, and the integrity of brain white matter tracts. CRT was assessed with a 4 CRT task on a separate occasion. Data were analyzed using multiple regression (N range = 358-670). RESULTS: Greater volume of hyperintensities and more severe hyperintensities in frontal regions were associated with higher CRT IIV. White matter tract integrity, as assessed by both fractional anisotropy and mean diffusivity, showed the smallest effect sizes in associations with CRT IIV. Associations with hyperintensities were attenuated and no longer significant after controlling for M CRT. CONCLUSIONS: Taken together, the results of the present study suggested that IIV was not incrementally predictive of white matter integrity over mean speed. This is in contrast to previous reports, and highlights the need for further study. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

20.
Twin Res Hum Genet ; 22(3): 131-139, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31250787

RESUMO

Higher health literacy is associated with higher cognitive function and better health. Despite its wide use in medical research, no study has investigated the genetic contributions to health literacy. Using 5783 English Longitudinal Study of Ageing (ELSA) participants (mean age = 65.49, SD = 9.55) who had genotyping data and had completed a health literacy test at wave 2 (2004-2005), we carried out a genome-wide association study (GWAS) of health literacy. We estimated the proportion of variance in health literacy explained by all common single nucleotide polymorphisms (SNPs). Polygenic profile scores were calculated using summary statistics from GWAS of 21 cognitive and health measures. Logistic regression was used to test whether polygenic scores for cognitive and health-related traits were associated with having adequate, compared to limited, health literacy. No SNPs achieved genome-wide significance for association with health literacy. The proportion of variance in health literacy accounted for by common SNPs was 8.5% (SE = 7.2%). Greater odds of having adequate health literacy were associated with a 1 standard deviation higher polygenic score for general cognitive ability [OR = 1.34, 95% CI (1.26, 1.42)], verbal-numerical reasoning [OR = 1.30, 95% CI (1.23, 1.39)], and years of schooling [OR = 1.29, 95% CI (1.21, 1.36)]. Reduced odds of having adequate health literacy were associated with higher polygenic profiles for poorer self-rated health [OR = 0.92, 95% CI (0.87, 0.98)] and schizophrenia [OR = 0.91, 95% CI (0.85, 0.96)). The well-documented associations between health literacy, cognitive function and health may partly be due to shared genetic etiology. Larger studies are required to obtain accurate estimates of SNP-based heritability and to discover specific health literacy-associated genetic variants.

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