Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

ObjectiveTo investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate.MethodsIn a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18–35 years; body mass index <28 kg/m2; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated.ResultsThe lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p<0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention.ConclusionHigher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes.Trial registration number NCT02355795; Results.

Background: Prospective cohort studies have examined mortality and overall cancer incidence among vegetarians, but the results have been inconclusive. Aims: The objective of the present meta-analysis was to investigate cardiovascular disease mortality and cancer incidence among vegetarians and nonvegetarians. Methods: Medline, EMBASE and Web Of Science databases were searched for cohort studies published from inception to September 2011. Studies were included if they contained the relative risk (RR) and corresponding 95% CI. Participants were from the UK, Germany, California, USA, the Netherlands and Japan. Results: Seven studies with a total of 124,706 participants were included in this analysis. All-cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66–1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56–0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54–1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70–1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67–0.97). Conclusions: Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancer incidence (18%) than nonvegetarians.

BackgroundVegetarian diets exclude all animal flesh and are being widely adopted by an increasing number of people; however, effects on blood lipid concentrations remain unclear. This meta‐analysis aimed to quantitatively assess the overall effects of vegetarian diets on blood lipids.Methods and ResultsWe searched PubMed, Scopus, Embase, ISI Web of Knowledge, and the Cochrane Library through March 2015. Studies were included if they described the effectiveness of vegetarian diets on blood lipids (total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and triglyceride). Weighted mean effect sizes were calculated for net changes by using a random‐effects model. We performed subgroup and univariate meta‐regression analyses to explore sources of heterogeneity. Eleven trials were included in the meta‐analysis. Vegetarian diets significantly lowered blood concentrations of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and non–high‐density lipoprotein cholesterol, and the pooled estimated changes were −0.36 mmol/L (95% CI −0.55 to −0.17; P<0.001), −0.34 mmol/L (95% CI −0.57 to −0.11; P<0.001), −0.10 mmol/L (95% CI −0.14 to −0.06; P<0.001), and −0.30 mmol/L (95% CI −0.50 to −0.10; P=0.04), respectively. Vegetarian diets did not significantly affect blood triglyceride concentrations, with a pooled estimated mean difference of 0.04 mmol/L (95% CI −0.05 to 0.13; P=0.40).ConclusionsThis systematic review and meta‐analysis provides evidence that vegetarian diets effectively lower blood concentrations of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and non–high‐density lipoprotein cholesterol. Such diets could be a useful nonpharmaceutical means of managing dyslipidemia, especially hypercholesterolemia.