Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence.

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Association of Neighborhood Deprivation With Epigenetic Aging Using 4 Clock Metrics.

Importance: Neighborhood deprivation is associated with age-related disease, mortality, and reduced life expectancy. However, biological pathways underlying these associations are not well understood. Objective: To evaluate the association between neighborhood deprivation and epigenetic measures of age acceleration and genome-wide methylation. Design, Setting, and Participants: This cross-sectional study used data from the Sister Study, a prospective cohort study comprising 50 884 women living in the US and Puerto Rico aged 35 to 74 years at enrollment who had a sister with breast cancer but had not had breast cancer themselves. Cohort enrollment occurred between July 2003 and March 2009. Participants completed a computer-assisted telephone interview on demographic, socioeconomic, lifestyle, and residential factors and provided anthropometric measures and peripheral blood samples at a home examination. DNA methylation data obtained for 2630 non-Hispanic White women selected for a case-cohort study in 2014 were used in this cross-sectional analysis. DNA methylation was measured using the HumanMethylation450 BeadChips in whole blood samples collected at baseline. Data analysis for this study was performed from October 17, 2019, to August 27, 2020. Exposures: Each participants' primary address was linked to an established index of neighborhood deprivation. Main Outcomes and Measures: Epigenetic age was estimated using 4 epigenetic clocks (Horvath, Hannum, PhenoAge, and GrimAge). Age acceleration was determined using residuals from regressing chronologic age on each of the 4 epigenetic age metrics. Linear regression was used to estimate associations between neighborhood deprivation and epigenetic age acceleration as well as DNA methylation at individual cytosine-guanine sites across the genome. Results: Mean (SD) age of the 2630 participants was 56.9 (8.7) years. Those with the greatest (>75th percentile) vs least (≤25th percentile) neighborhood deprivation had higher epigenetic age acceleration estimated by Hannum (ß = 0.23; 95% CI, 0.01-0.45), PhenoAge (ß = 0.28; 95% CI, 0.06-.50), and GrimAge (ß = 0.37; 95% CI, 0.12-0.62). Increasing US quartiles of neighborhood deprivation exhibited a trend with Hannum, PhenoAge, and GrimAge. For example, GrimAge showed a significant dose-response (P test for trend <.001) as follows: level 2 vs level 1 (ß = 0.30; 95% CI, 0.17-0.42), level 3 vs level 1 (ß = 0.35; 95% CI, 0.19-0.50), and level 4 vs level 1 (ß = 0.37; 95% CI, 0.12-0.62). Neighborhood deprivation was found to be associated with 3 cytosine-phosphate-guanine sites, with 1 of these annotated to a known gene MAOB (P = 9.71 × 10-08). Conclusions and Relevance: The findings of this study suggest that residing in a neighborhood with a higher deprivation index appears to be reflected by methylation-based markers of aging.

Millisecond, micron precision multi-whisker detector.

The neural mechanisms of somatosensory information processing in the rodent vibrissae system are a topic of intense debate and research. Certain hypotheses emphasize the importance of stick-slip whisker motion, high-frequency resonant vibrations, and/or the ability to decode complex textures. Other hypotheses focus on the importance of integrating information from multiple whiskers. Tests of the former require measurements of whisker motion that achieve high spatiotemporal accuracy without altering the mechanical properties of whiskers. Tests of the latter require the ability to monitor the motion of multiple whiskers simultaneously. Here we present a device that achieves both these requirements for two-dimensional whisker motion in the plane perpendicular to the whiskers. Moreover, the system we present is significantly less expensive (<$2.5 k) and simpler to build than alternative devices which achieve similar detection capabilities. Our system is based on two laser diodes and two linear cameras. It attains millisecond temporal precision and micron spatial resolution. We developed automated algorithms for processing the data collected by our device and benchmarked their performance against manual detection by human visual inspection. By this measure, our detection was successful with less than 10 µm deviation between the automated and manual detection, on average. Here, we demonstrate its utility in anesthetized rats by measuring the motion of multiple whiskers in response to an air puff.