DNA methylation-based estimator of telomere length

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

Successful explanations start with accurate descriptions: Questionnaire items as personality markers for more accurate predictions

Personality-outcome associations, typically represented using the Big Five personality domains, are ubiquitous, but often weak and possibly driven by the constituents of these domains. We hypothesized that representing the associations using personality questionnaire items (as markers for personality nuances) could increase prediction strength. Using the National Child Development Study (N = 8,719), we predicted 40 diverse outcomes from both the Big Five domains and their 50 items. Models were trained (using penalized regression) and applied for prediction in independent sample partitions (with 100 permutations). Item-models tended to out-predict Big Five-models (explaining on average 30% more variance), regardless of outcomes’ independently-rated breadth versus behavioral specificity. Moreover, the predictive power of Big Five domains per se was at least partly inflated by the unique variance of their constituent items, especially for generally more predictable outcomes. Removing the Big Five variance from items marginally reduced their predictive power. These findings are consistent with the possibility that the associations of personality with outcomes often pertain to (potentially large numbers of) specific behavioral, cognitive, affective and motivational characteristics represented by single questionnaire items rather than to the broader (underlying) traits that these items are ostensibly indicators of. This may also have implications for personality-based interventions

The finer details? The predictability of life outcomes from Big Five domains, facets, and nuances

Associations between personality traits and life outcomes are usually studied using the Big Five domains and, occasionally, their facets. But recent research suggests these associations may be driven by the items (reflecting nuances) chosen to measure these traits. Using a large dataset (N = 6,126), we examined associations with 53 self-reported outcomes using domains, facets and items (markers for nuances), training and validating models in different sample partitions. Facets better predicted outcomes than domains (on average, 18.0% vs 16.6% of variance explained), but items provided the most accurate predictions (on average 20.9%). Removing domain and facet variance from items had no effect on their predictive validity, suggesting that outcome-related information was present in items’ unique variances (nuances). Item-based prediction also showed the highest outcome-specificity (discriminant validity). These observations, replicating previous indications, suggest that personality traits’ associations with outcomes are often driven by narrow personality nuances

Epigenome-wide association study of leukocyte telomere length

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

Genetic and epigenetic architectures of neurological protein biomarkers in the Lothian Birth Cohort 1936 - EWAS

Data supporting the paper Hillary et al. "Genetic and epigenetic architectures of neurological protein biomarkers in the Lothian Birth Cohort 1936" (In submission). Specifically EWAS proteins.Hillary, Robert; McCartney, Daniel; Harris, Sarah; Stevenson, Anna; Seeboth, Anne; Zhang, Qian; Liewald, David; Evans, Kathryn; Ritchie, Craig; Tucker-Drob, Elliot; Wray, Naomi; McRae, Allan; Visscher, Peter; Deary, Ian; Marioni, Riccardo. (2019). Genetic and epigenetic architectures of neurological protein biomarkers in the Lothian Birth Cohort 1936 - EWAS, 1936-2019 [dataset]. University of Edinburgh. Centre for Cognitive Ageing and Cognitive Epidemiology