Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.

No abstract

Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.

Crosstalk between «/ß T-cells and 7/8 T-cells in vivo: Activation of ot/[3 T-cell responses after 7/fi T-cell modulation with the monoclonal antibody GL3. ftv c Natl Acad Sci USA 1993; 90: 9620-24. 29 Munk E, Gatrill AJ, Kaufmann SHE. Target cell lysis and IL-2 secretion by 7/ft T lymphocytes after activation with bacteria.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

No abstract

Age-adjusted mortality is reduced 2% with each increasing year of age at menopause. In particular, ischemic heart disease mortality is 2% lower. Although the risk of death from uterine or ovarian cancer is increased by 5%, the net effect of a later menopause is an increased lifespan.

Objective: To determine the incidence and prevalence of facioscapulohumeral muscular dystrophy (FSHD) in the Netherlands.Methods: Using 3-source capture-recapture methodology, we estimated the total yearly number of newly found symptomatic individuals with FSHD, including those not registered in any of the 3 sources. To this end, symptomatic individuals with FSHD were available from 3 large populationbased registries in the Netherlands if diagnosed within a 10-year period (January 1, 2001 to December 31, 2010). Multiplication of the incidence and disease duration delivered the prevalence estimate.Results: On average, 52 people are newly diagnosed with FSHD every year. This results in an incidence rate of 0.3/100,000 person-years in the Netherlands. The prevalence rate was 12/100,000, equivalent to 2,000 affected individuals.Conclusions: We present population-based incidence and prevalence estimates regarding symptomatic individuals with FSHD, including an estimation of the number of symptomatic individuals not present in any of the 3 used registries. This study shows that the total number of symptomatic persons with FSHD in the population may well be underestimated and a considerable number of affected individuals remain undiagnosed. This suggests that FSHD is one of the most prevalent neuromuscular disorders. Recently, a unifying genetic model of facioscapulohumeral muscular dystrophy (FSHD) was described, thereby facilitating identification of potential therapeutic targets.1 As clinical studies on FSHD interventions can be expected in the near future, accurate data on FSHD epidemiology are needed for trial readiness.Several studies reported on FSHD epidemiology (figure 1, table e-1 on the Neurology ® Web site at Neurology.org); 4 were performed after genetic testing became available but did not report on population-based incidence estimates.2 In the Netherlands, people newly diagnosed with a neuromuscular disorder are registered nationwide by 7 neuromuscular centers in CRAMP (Computer Registry of all Myopathies and Polyneuropathies).3 This registry provides an opportunity to study frequencies of FSHD among the Dutch population.FSHD frequencies are prone to underestimation because this disease is characterized by a high degree of clinical variability with a large proportion of individuals with mild symptoms. Moreover, relatives of persons diagnosed with FSHD may not seek medical attention. 4 We used capturerecapture methodology to estimate the total number of symptomatic individuals with FSHD by combining CRAMP data with 2 other large population-based registries. This includes those not *These authors contributed equally.