Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease

Background The Tehran Lipid and Glucose Study (TLGS) is a long term integrated community-based program for prevention of non-communicable disorders (NCD) by development of a healthy lifestyle and reduction of NCD risk factors. The study begun in 1999, is ongoing, to be continued for at least 20 years. A primary survey was done to collect baseline data in 15005 individuals, over 3 years of age, selected from cohorts of three medical heath centers. A questionnaire for past medical history and data was completed during interviews; blood pressure, pulse rate, and anthropometrical measurements and a limited physical examination were performed and lipid profiles, fasting blood sugar and 2-hours-postload-glucose challenge were measured. A DNA bank was also collected. For those subjects aged over 30 years, Rose questionnaire was completed and an electrocardiogram was taken. Data collected were directly stored in computers as database software- computer assisted system. The aim of this study is to evaluate the feasibility and effectiveness of lifestyle modification in preventing or postponing the development of NCD risk factors and outcomes in the TLGS population. Design and methods In phase II of the TLGS, lifestyle interventions were implemented in 5630 people and 9375 individuals served as controls. Primary, secondary and tertiary interventions were designed based on specific target groups including schoolchildren, housewives, and high-risk persons. Officials of various sectors such as health, education, municipality, police, media, traders and community leaders were actively engaged as decision makers and collaborators. Interventional strategies were based on lifestyle modifications in diet, smoking and physical activity through face-to-face education, leaflets & brochures, school program alterations, training volunteers as health team and treating patients with NCD risk factors. Collection of demographic, clinical and laboratory data will be repeated every 3 years to assess the effects of different interventions in the intervention group as compared to control group. Conclusion This controlled community intervention will test the possibility of preventing or delaying the onset of non-communicable risk factors and disorders in a population in nutrition transition. Trial registration ISRCTN52588395

Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.