There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined approximately 2,000 individuals for each of 7 major diseases and a shared set of approximately 3,000 controls. Case-control comparisons identified 24 independent association signals at

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

chemical findings stable. The packed cell volume was 0 27. With hypertonic peritoneal dialysis his weight decreased by 1 6 kg, but blood pressure remained raised at 230/130 mm Hg, and the next day he suffered two generalised seizures. Packed cell volume was 0-35. Phenytoin was started. He was discharged on 17 December, normotensive with no neurological sequelae, and taking no antihypertensive medication. Phenytoin was subsequently withdrawn. He had a cadaveric renal transplant in 1987 and remained well with a blood pressure of 130/80 mm Hg. CommentNeither patient had previously suffered seizures. In both fitting occurred after a sudden rise in blood pressure in association with normal fundi and computed tomograms and in the context of recent blood transfusion and increase in packed cell volume. These features closely resemble those of seizures reported in patients treated with erythropoietin while undergoing dialysis.2 As with erythropoietin, the factors precipitating fits in these patients remain unclear. In case 1 the haemoconcentration associated with haemodialvsis may have been relevant. The second patient was not fluid overloaded at the time of the first seizure but was at the time of the second, when rapid fluid removal by peritoneal dialysis might have contributed. Perhaps a rapid rise in packed cell volume resulted in both increased blood viscosity and a loss of hypoxic vasodilatationt and thus a rise in vascular resistance. Subjects, methods, and results I studied the epidemiology of hay fever in a national sample of 17 414 British children born during one week in March 1958 and followed up to the age of 23 years (the National Child Development Study). Three outcomes were investigated: (a) self reported "hay fever during the past 12 months" at age 23; (b) parental report of "hay fever or allergic rhinitis in the past 12 months" at age 11; (c) parental recall of "eczema in the first year of life" elicited when the child was 7. Cross tabulations were performed with the SAS statistical package, and multiple logistic regression models were fitted with the LR program in the BMDP statistical package.Of the 16 perinatal, social, and environmental factors studied the most striking associations with hay fever were those for family size and position in the household in childhood. The table shows that at both 11 and 23 years of age hay fever was inversely related to the number of children in the household at age 11 (when it is assumed most families were complete). When prevalence figures were adjusted by multiple logistic regression for other significant determinants of hay fever in this cohort (see table) the associations with numbers ofolder and younger children in the household persisted. These trends in adjusted prevalence were independent of one another and each was significant (p<001, see

Obesity is globally prevalent and highly heritable, but the underlying genetic factors remain largely elusive. To identify genetic loci for obesity-susceptibility, we examined associations between body mass index (BMI) and ~2.8 million SNPs in up to 123,865 individuals, with targeted follow-up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity-susceptibility loci and identified 18 new loci associated with BMI (P<5×10−8), one of which includes a copy number variant near GPRC5B. Some loci (MC4R, POMC, SH2B1, BDNF) map near key hypothalamic regulators of energy balance, and one is near GIPR, an incretin receptor. Furthermore, genes in other newly-associated loci may provide novel insights into human body weight regulation.

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