Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years

Increases in aortic pulse wave velocity, a measure of arterial stiffness, can lead to elevated systolic blood pressure and increased cardiac afterload in adulthood. These changes are detectable in childhood and potentially originate in utero, where an adverse early life environment can alter DNA methylation patterns detectable at birth. Here, analysis of epigenome-wide methylation patterns using umbilical cord blood DNA from 470 participants in the Southampton’s Women’s Survey identified differential methylation patterns associated with systolic blood pressure, pulse pressure, arterial distensibility, and descending aorta pulse wave velocity measured by magnetic resonance imaging at 8 to 9 years. Perinatal methylation levels at 16 CpG loci were associated with descending aorta pulse wave velocity, with identified CpG sites enriched in pathways involved in DNA repair (P=9.03×10−11). The most significant association was with cg20793626 methylation (within protein phosphatase, Mg2+/Mn2+ dependent 1D; β=−0.05 m/s/1% methylation change, [95% CI, −0.09 to −0.02]). Genetic variation was also examined but had a minor influence on these observations. Eight pulse wave velocity-linked dmCpGs were associated with prenatal modifiable risk factors, with cg08509237 methylation (within palmitoyl-protein thioesterase-2) associated with maternal oily fish consumption in early and late pregnancy. Lower oily fish consumption in early pregnancy modified the relationship between methylation and pulse wave velocity, with lower consumption strengthening the association between cg08509237 methylation and increased pulse wave velocity. In conclusion, measurement of perinatal DNA methylation signatures has utility in identifying infants who might benefit from preventive interventions to reduce risk of later cardiovascular disease, and modifiable maternal factors can reduce this risk in the child

Feed intake and production parameters of lactating crossbred cows fed maize-based diets of stover, silage or quality protein silage

Thirty-six Boran × Friesian dairy cows (392 ± 12 kg; mean ± SD) in early parity were used in a randomised complete block design. Cows were blocked by parity into three blocks of 12 animals and offered normal maize (NM) stover (T1), NM silage (T2) or quality protein maize (QPM) silage (T3) basal diets supplemented with a similar concentrate mix. Feed intake, body weight and condition changes and milk yield and composition were assessed. The daily intake of DM, OM, NDF and ADF for cows fed the NM stover-based diet was higher (P < 0.05) than for the cows fed the NM silage and QPM silage-based diets. However, the daily intake of DOM (9.3 kg) and ME (140.8 MJ) for cows on QPM silage-based diet was higher (P < 0.05) than for cows on NM stover-based diet (8.4 kg and 124.2 MJ) and NM silage-based diet (7.9 kg and 119.1 MJ). Body weight of cows was affected (P < 0.05) by the diet, but diet had no effect (P > 0.05) on body condition score, milk yield and milk composition. The digestible organic matter in the NM stover-based diet (724 g/kg DM) was lower (P < 0.05) than that in the NM (770 g/kg DM) and QPM silage-based diet (762 g/kg DM). It was concluded that the performances of the cows on the NM silage and QPM silage diets were similar and were not superior to that of the NM stover-based diet

A meta-analysis of genome-wide association studies of childhood wheezing phenotypes identifies ANXA1 as a susceptibility locus for persistent wheezing

BACKGROUND: Many genes associated with asthma explain only a fraction of its heritability. Most genome-wide association studies (GWASs) used a broad definition of 'doctor-diagnosed asthma', thereby diluting genetic signals by not considering asthma heterogeneity. The objective of our study was to identify genetic associates of childhood wheezing phenotypes. METHODS: We conducted a novel multivariate GWAS meta-analysis of wheezing phenotypes jointly derived using unbiased analysis of data collected from birth to 18 years in 9568 individuals from five UK birth cohorts. RESULTS: Forty-four independent SNPs were associated with early-onset persistent, 25 with pre-school remitting, 33 with mid-childhood remitting, and 32 with late-onset wheeze. We identified a novel locus on chr9q21.13 (close to annexin 1 [ANXA1], p<6.7 × 10-9), associated exclusively with early-onset persistent wheeze. We identified rs75260654 as the most likely causative single nucleotide polymorphism (SNP) using Promoter Capture Hi-C loops, and then showed that the risk allele (T) confers a reduction in ANXA1 expression. Finally, in a murine model of house dust mite (HDM)-induced allergic airway disease, we demonstrated that anxa1 protein expression increased and anxa1 mRNA was significantly induced in lung tissue following HDM exposure. Using anxa1-/- deficient mice, we showed that loss of anxa1 results in heightened airway hyperreactivity and Th2 inflammation upon allergen challenge. CONCLUSIONS: Targeting this pathway in persistent disease may represent an exciting therapeutic prospect. FUNDING: UK Medical Research Council Programme Grant MR/S025340/1 and the Wellcome Trust Strategic Award (108818/15/Z) provided most of the funding for this study

Constraints on the Timing of Explosive Volcanism at Aso and Aira Calderas (Japan) Between 50 and 30 ka: New Insights From the Lake Suigetsu Sedimentary Record (SG14 Core)

Volcanoes in the East Asian/Pacific region have been the source of some of the largest magnitude eruptions during the Quaternary, and accurately evaluating their eruptive histories is essential for hazard assessments. To overcome difficulties in resolving and precisely dating eruptions in the near‐source realm, the high‐resolution (varved) sediments of Lake Suigetsu (central Honshu, Japan) were examined for the presence of non‐visible (cryptotephra) layers from 50 ka up until the 30 ka AT caldera‐forming event of Aira volcano. Cryptotephra layers are four times more frequently preserved than visible markers in the Suigetsu sediments, meaning that this archive provides a unique and unprecedented record of eruptions that were dispersed towards the densely populated regions of central Honshu. Major and trace element volcanic glass chemistry is used to fingerprint the ash layers and pinpoint their volcanic origin. Tephras are found throughout the investigated sediments, but the highest abundance of ash fall events are recorded between 39 and 30 ka, capturing a period of intense volcanism at calderas on Kyushu Island (Japan). The augmented Suigetsu tephrostratigraphy records at least seven eruption events from Aso caldera (southern Kyushu) that post‐date the widespread ACP‐4 Plinian eruption (ca. 50 ka), and four explosive events from Aira (central Kyushu) that occurred leading up to the catastrophic caldera‐forming AT eruption (ca. 30 ka)

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (née European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60 % from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019)Swiss National Science Foundation | Ref. 200021_16959

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (nee European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60% from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019).Peer reviewe

Refining the eruptive history of Ulleungdo and Changbaishan volcanoes (East Asia) over the last 86 kyrs using distal sedimentary records

The eruptive histories of Ulleungdo (South Korea) and Changbaishan (North Korea/China border) volcanoes are not well constrained since their proximal stratigraphies are poorly exposed or largely inaccessible. However, determining the past behaviour of these volcanoes is critical since future eruptions are likely to disperse ash over some of the world’s largest metropolitan regions. Alkaline tephra deposits erupted from both centres are routinely identified in marine cores extracted from the Sea of Japan, as well as high-resolution lacustrine records east of the volcanoes. Here, we review the distal ash occurrences derived from Ulleungdo and Changbaishan and provide new data from the Lake Suigetsu (central Honshu, Japan) sediment core, in order to provide a more complete and constrained eruption framework. The intensely-dated Lake Suigetsu archive provides one of the most comprehensive distal eruption records for both centres, despite being located ca. 500 km E of Ulleungdo and ca. 1000 km SSE of Changbaishan. The Suigetsu record is utilised to precisely date and geochemically fingerprint (using major, minor and trace element glass compositions) ash fall events that reached central Honshu. Here, we identify a new non-visible (cryptotephra) layer in the Suigetsu sediments, which reveals a previously unreported explosive event from Changbaishan at 42,750 – 42,323 IntCal13 yrs BP (95.4 % confidence interval). This event is chronologically and geochemically distinct from the B-J (Baegdusan-Japan Basin) tephra reported in the Sea of Japan (ca. 50 ka). Furthermore, we also confirm that the widespread U-Ym tephra erupted from Ulleungdo reached central Japan, and is herein dated to 40,332 – 39,816 IntCal13 yrs BP (95.4 % confidence interval). This terrestrial 14C-derived age of the U-Ym can be used to constrain the chronology of marine records containing the same marker layer. This reviewed and integrated tephrostratigraphic framework highlights the pivotal role that distal sedimentary records can play in evaluating the eruptive histories and hazard potential of Ulleungdo and Changbaishan

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Blood samples and raw genetic data of neonatal subjects from each cohort are governed by their respective institutions and/or government agencies, and mostly could not be shared publicly without specific approvals. For example, for data from first author cohort, California Childhood Leukemia Study (CCLS), we respectfully are unable to share raw, individual genetic data freely with other investigators. Should we be contacted by other investigators who would like to use the data; we will direct them to the California Department of Public Health Institutional Review Board to establish their own approved protocol to utilize the data, which can then be shared peer-to-peer.Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.National Institute of Environmental Health SciencesNational Cancer InstituteUS Environmental Protection Agenc

Integrating the Holocene tephrostratigraphy for East Asia using a high-resolution cryptotephra study from Lake Suigetsu (SG14 core), central Japan

Tephra (volcanic ash) layers have the potential to synchronise disparate palaeoenvironmental archives on regional to hemispheric scales. Highly productive arc regions, like those in East Asia, offer a considerable number of widespread isochrons, but before records can be confidently correlated using these layers, a refined and integrated framework of these eruptive events is required. Here we present the first high-resolution Holocene cryptotephra study in East Asia, using the Lake Suigetsu sedimentary archive in central Japan. The Holocene tephrostratigraphy has been extended from four to twenty ash layers using cryptotephra extraction techniques, which integrates the deposits from explosive eruptions from North Korea/China, South Korea and along the Japanese arc. This Lake Suigetsu tephrostratigraphy is now the most comprehensive record of East Asian volcanism, and the linchpin site for correlating sequences across this region. Major element glass geochemical compositions are presented for the tephra layers in the sequence, which have been compared to proximal datasets to correlate them to their volcanic source and specific eruptions. This study has significantly extended the ash dispersal of many key Holocene marker layers, and has identified the first distal occurrence of isochrons from Ulleungdo and Changbaishan volcanoes. Utilising the high-precision Lake Suigetsu chronology, we are able to provide constrained eruption ages for the tephra layers, which can be transferred into other site-specific age models containing these markers. This new framework indicates that several isochrons stratigraphically bracket abrupt climate intervals in Japan, and could be used to precisely assess the regional and hemispheric synchronicity of these events