Alcohol Intake and Total Mortality in 142,960 Individuals from the MORGAM Project: a population-based study

To test the association of alcohol consumption with total and cause-specific mortality risk DESIGN: Prospective observational multicentre population-based study SETTING: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project PARTICIPANTS: A total of 142,960 individuals (mean age 50\ub113 y, 53.9% men) MEASUREMENTS: Average alcohol intake by food frequency questionnaire. Total and cause-specific mortality FINDINGS: In comparison with lifetime abstainers, consumption of alcohol less than 10 gr/d was associated with an average 11% (95%CI: 7%-14%) reduction in the risk of total mortality, while intake >20 gr/d was associated with a 13% (7%-20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. As far as cancer is concerned, drinking up to 10 gr/d was not associated with either mortality risk reduction or increase, while alcohol intake >20 gr/d was associated with a 22% (10%-35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between Countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that HDLc explained 2.9% and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively

Alcoholic beverage preference and diabetes incidence across Europe: The Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project

Background/Objectives:It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol.Subjects/Methods:Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when 6570% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis.Results:Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: Pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases.Conclusions:This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference. \ua9 2017 Macmillan Publishers Limited, part of Springer Nature

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals

Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant)