The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes. Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension. Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Nutrition-related chronic diseases such as cardiovascular diseases and cancer are of multiple origin, and may be due to genetic, biologic, behavioural and environmental factors. In order to detangle the specific role of nutritional factors, very large population sample cohort studies comprising precisely measured dietary intake and all necessary information for accurately assessing potential confounding factors are needed. Widespread use of internet is an opportunity to gradually collect huge amounts of data from a large sample of volunteers that can be automatically verified and processed. The objectives of the NutriNet-Santé study are: 1) to investigate the relationship between nutrition (nutrients, foods, dietary patterns, physical activity), mortality and health outcomes; and 2) to examine the determinants of dietary patterns and nutritional status (sociological, economic, cultural, biological, cognitive, perceptions, preferences, etc.), using a web-based approach. Our web-based prospective cohort study is being conducted for a scheduled follow-up of 10 years. Using a dedicated web site, recruitment will be carried out for 5 years so as to register 500 000 volunteers aged ≥ 18 years among whom 60% are expected to be included (having complete baseline data) and followed-up for at least 5 years for 240 000 participants. Questionnaires administered via internet at baseline and each year thereafter will assess socio-demographic and lifestyle characteristics, anthropometry, health status, physical activity and diet. Surveillance of health events will be implemented via questionnaires on hospitalisation and use of medication, and linkage with a national database on vital statistics. Biochemical samples and clinical examination will be collected in a subsample of volunteers. Self-administered data collection using internet as a complement to collection of biological data will enable identifying nutrition-related risks and protective factors, thereby more clearly elucidating determinants of nutritional status and their interactions. These are necessary steps for further refining nutritional recommendations aimed at improving the health status of populations.