A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management.

DNA methylation-based measures of accelerated biological ageing and the risk of dementia in the oldest-old: a study of the Lothian Birth Cohort 1921.

BACKGROUND: Previous studies have demonstrated an association between DNA methylation-based measures of accelerated ageing and age-related health outcomes and mortality. As a disease closely associated with advancing age, we hypothesized that DNA methylation-based measures of accelerated ageing might be associated with risk for dementia. This study therefore aimed to examine the association between four recognised measures of age acceleration and subsequent dementia. METHODS: Study subjects (n = 488) were members of the Lothian Birth Cohort 1921. Dementia case ascertainment used data from death certificates, electronic hospital records, and clinical reviews. Venous blood samples were taken at baseline, at age 79 years. DNA methylation and measures of epigenetic age were calculated in accordance with Horvath's epigenetic clock tutorial, using the online calculator (https://dnamage.genetics.ucla.edu/). From these values, four measures of accelerated ageing were calculated: extrinsic epigenetic age acceleration (EEAA), intrinsic epigenetic age acceleration (IEAA), AgeAccelPheno and AgeAccelGrim. Competing risk regression models - with death as a competing risk - were performed to examine the association between each measure of accelerated ageing and incident dementia. APOE ɛ4 status, sex, age, smoking status, history of cardiovascular disease, cerebrovascular disease, hypertension, and diabetes were included as covariates. RESULTS: None of the multivariate models revealed a positive association between increased epigenetic age acceleration and dementia risk. Across all included models, never-smoking increased risk for dementia (HR 1.69 [1.06, 2.71], p = 0.03), and having no APOE ɛ4 alleles reduced risk for dementia (HR 0.44 [0.29, 0.67], p < 0.001). CONCLUSIONS: The present study did not demonstrate any consistent association between DNA methylation-based measures of accelerated ageing and dementia in subjects aged over 79 years. Further, larger studies - including separate analyses of dementia subtypes - are required to further investigate the potential association between DNA methylation-based measures of accelerated ageing and dementia.

Cognitive function in early and later life is associated with blood glucose in older individuals: analysis of the Lothian Birth Cohort of 1936.

AIMS/HYPOTHESIS: The aim of this study was to examine whether cognitive function in early and later life, and decline in cognitive function from age 70 to 79 years, are associated with high blood glucose, as measured by HbA1c, at baseline (age 70), and changes in blood glucose from age 70 to 79. METHODS: Participants (n = 1091) in the Lothian Birth Cohort of 1936 were examined. Fourteen tests were used to assess cognitive functions, grouped into four domains: visuospatial ability, processing speed, memory and crystallised ability. Test results, and measurements of HbA1c and other health variables, were collected at each of four waves of assessment: at the mean age of 70, 73, 76 and 79 years. Data on cognitive function at age 11 was also available for this cohort. Latent growth curve modelling was performed and statistical controls for known risk factors were introduced. RESULTS: Higher age 11 cognitive function predicted lower HbA1c level at age 70 (p < 0.001). Higher cognitive function at age 70 was related to a comparatively smaller increase in HbA1c levels from age 70 to 79 (p < 0.001). HbA1c from age 70 to 79 did not have any consistent association with change in cognitive function from age 70 to 79. These associations survived adjustments for age, sex, education, APOE*ε4, smoking history, cardiovascular disease history, hypertension history, BMI and corrections for multiple testing. CONCLUSIONS/INTERPRETATION: Our results show that, among older individuals, high blood glucose is consistently predicted by lower cognitive function. Clinical care that examines and tracks cognitive function, while also taking the positive effects of maintaining cognitive function and emulating healthy behaviours associated with higher cognitive function into account, may be one approach for protecting at-risk individuals from elevated blood glucose and subsequent type 2 diabetes mellitus.