New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475,000 Individuals

Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant. Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up

Orbital-scale benthic foraminiferal oxygen isotope stratigraphy at the northern Bering Sea Slope Site U1343 (IODP Expedition 323) and its Pleistocene paleoceanographic significance

A continuous composite oxygen isotope (δ18O) stratigraphy from benthic foraminifera in the Bering Sea was reconstructed in order to provide insight into understanding sea-ice evolution in response to Northern Hemisphere Glaciation. Oxygen isotope records from multiple species of benthic foraminifera at Integrated Ocean Drilling Program (IODP) Expedition 323 Site U1343 (54°33.4'N, 176°49.0'E, water depth 1950 m) yield a highly refined orbital-scale age model spanning the last 1.2 Ma, and a refined age model between 1.2 and 2.4 Ma. An inter-species calibration was used to define species offsets and to successfully obtain a continuous composite benthic δ18O record, correlated with the global composite benthic δ18O stack curve LR04 to construct an orbital-scale age model. The consistency of the benthic δ18O stratigraphy with biostratigraphy and magnetostratigraphy confirms the reliability of both methods for constraining age. The time difference between cyclic changes in sedimentary physical properties and glacial–interglacial cycles since 0.8 Ma is notable, and suggests that physical properties alone cannot be used to construct an orbital-scale age model. Amplitude changes in physical properties and a significant drop in the linear sedimentation rate during glacials after 0.9 Ma indicate that the glacial sea-ice edge extended beyond the Bering Sea Slope (Site U1343) at this time

Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition.

Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR = 1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR = 1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction = 0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear

Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European Prospective Investigation into Cancer-Eurgast cohort

Public Health and primary carePrevention, Population and Disease management (PrePoD

Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European prospective investigation into cancer and nutrition

Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79–0.97 and 0.76; 95% CI 0.62–0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be exclude

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

Item does not contain fulltextCarotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (alpha- and beta-carotene, canthaxanthin, beta-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (alpha-, beta- and gamma- and delta-tocopherol) and dietary consumption of beta-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary beta-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties