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.

The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85×10−8 in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84×10−7), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at ∼1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults.

Aims: To investigate the association between climate and atopic diseases using worldwide data from 146 centres of the International Study of Asthma and Allergies in Childhood (ISAAC). Methods: Between 1992 and 1996, each centre studied random samples of children aged 13-14 and 6-7 years (approx. 3000 per age group and centre) using standardised written and video questionnaires on symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema during the past 12 months. Data on long term climatic conditions in the centres were abstracted from one standardised source, and mixed linear regression models calculated to take the clustering of centres within countries into account. Results: In Western Europe (57 centres in 12 countries), the prevalence of asthma symptoms, assessed by written questionnaire, increased by 2.7% (95% CI 1.0% to 4.5%) with an increase in the estimated annual mean of indoor relative humidity of 10%. Similar associations were seen for the video questionnaire and the younger age group. Altitude and the annual variation of temperature and relative humidity outdoors were negatively associated with asthma symptoms. The prevalence of eczema symptoms correlated with latitude (positively) and mean annual outdoor temperature (negatively). Conclusions: Results suggest that climate may affect the prevalence of asthma and atopic eczema in children.A potential role of climatic conditions in the aetiology of asthma and allergies has long been suspected.