Fish, Marine n−3 Fatty Acids, and Atrial Fibrillation – Experimental Data and Clinical Effects

Marine n−3 polyunsaturated fatty acids (PUFA) may have beneficial effects in relation to atrial fibrillation (AF) with promising data from experimental animal studies, however, results from studies in humans have been inconsistent. This review evaluates the mechanisms of action of marine n−3 PUFA in relation to AF based on experimental data and provides a status on the evidence obtained from observational studies and interventional trials. In conclusion, there is growing evidence for an effect of marine n−3 PUFA in prevention and treatment of AF. However, further studies are needed to establish which patients are more likely to benefit from n−3 PUFA, the timing of treatment, and dosages

A Mendelian randomization study of circulating uric acid and type 2 diabetes

We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid associated loci. We used data of the EPIC-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident type 2 diabetes cases were ascertained. Higher uric acid associated with higher diabetes risk following adjustment for confounders, with a HR of 1.20 (95%CI: 1.11,1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95%CI: 15,18) per SD increase, and explained 4% of uric acid variation. Using the genetic score to estimate the unconfounded effect found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01, 95%CI: 0.87,1.16). Including data from DIAGRAM consortium, increasing our dataset to 41,508 diabetes cases, the summary OR estimate was 0.99 (95%CI: 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid lowering therapies may therefore not be beneficial in reducing diabetes risk

Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.

BACKGROUND: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. METHODS AND FINDINGS: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. CONCLUSIONS: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following sources: Medical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5, and Medical Research Council Human Nutrition Research MC_UP_A090_1006 and Cambridge Lipidomics Biomarker Research Initiative G0800783; FLC and TJK: Cancer Research UK; JMH and MJT: Health Research Fund of the Spanish Ministry of Health; Murcia Regional Government (Nº 6236); MG: Regional Government of Navarre; -IS, DLvdA, AMWS, YTvdS: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; Verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); KTK: Medical Research Council UK, Cancer Research UK; PMN: Swedish Research Council; KO and AT: Danish Cancer Society; JRQ: Asturias Regional Government; OR: The Västerboten County Council; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

Data resource profile:the Aarhus birth cohort biobank (ABC biobank)

Exposure during fetal life may have long-lasting health consequences for the child. Cohorts with biological material are necessary to investigate the possible biological mechanisms behind this potential early programming of disease. The Aarhus Birth Cohort Biobank was established in 2008 as an amendment to an ongoing research database, the Aarhus Birth Cohort. It aims to provide the opportunity to investigate the role of genetic factors, environmental exposures and lifestyles in pregnancy on the risk of disease in the offspring. All pregnant women who plan to give birth at Aarhus University Hospital, Skejby, and the fathers-to-be are invited to participate in the Aarhus Birth Cohort Biobank. Blood samples (mother 54 ml, father 4 ml) are drawn at the time of the routine ultrasound scanning in gestational week 12. At the same time, the women fill out a detailed questionnaire on medical and lifestyle factors. Immediately after birth, blood (10 ml) from the umbilical cord and umbilical cord tissue are sampled. Samples from the mothers are separated into plasma, buffy coat, erythrocyte suspension and serum before freezing at -80°C. Samples of whole blood are also stored, from both the mother and the father. Plasma, buffy coat, erythrocyte suspension and tissue from the umbilical cord are stored at -80°C. All researchers can apply for access to the database. For more details, see. www.ab-biobank.dk or. [email protected]. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2013; all rights reserved

Long-chain n-3 and n-6 polyunsaturated fatty acids and risk of atrial fibrillation: results from a Danish cohort study

BackgroundStudies of the relation between polyunsaturated fatty acids and risk of atrial fibrillation have been inconclusive. The risk of atrial fibrillation may depend on the interaction between n-3 and n-6 polyunsaturated fatty acids as both types of fatty acids are involved in the regulation of systemic inflammation.ObjectiveWe investigated the association between dietary intake of long chain polyunsaturated fatty acids (individually and in combination) and the risk of atrial fibrillation with focus on potential interaction between the two types of polyunsaturated fatty acids.DesignThe risk of atrial fibrillation in the Diet, Cancer and Health Cohort was analyzed using the pseudo-observation method to explore cumulative risks on an additive scale providing risk differences. Dietary intake of long chain polyunsaturated fatty acids was assessed by food frequency questionnaires. The main analyses were adjusted for the dietary intake of n-3 α-linolenic acid and n-6 linoleic acid to account for endogenous synthesis of long chain polyunsaturated fatty acids. Interaction was assessed as deviation from additivity of absolute association measures (risk differences).ResultsCumulative risks in 15-year age periods were estimated in three strata of the cohort (N = 54,737). No associations between intake of n-3 or n-6 long chain polyunsaturated fatty acids and atrial fibrillation were found, neither when analyzed separately as primary exposures nor when interaction between n-3 and n-6 long chain polyunsaturated fatty acids was explored.ConclusionThis study suggests no association between intake of long chain polyunsaturated fatty acids and risk of atrial fibrillation