Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10−8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

T here is much scientific evidence to warrant that the regional distribution of body fat is an important consideration in the relationship between obesity, metabolism, and health. Although recent evidence from several prospective studies has demonstrated significant associations between regional body fat distribution and cardiovascular disease (CVD) and related mortality, 1 -8 the mechanisms responsible for this relationship have yet to be established. Numerous reports in the literature have confirmed the early clinical observations of Vague 8 and have shown that the topography of adipose tissue (AT) was associated with metabolic complications that are considered to be risk factors for cardiovascular disease From the Physical Activity Sciences Laboratory, Laval University, and the LJpid and Diabetes Research Units,

We undertook this study to determine whether there are differences in the responses of different persons to long-term overfeeding and to assess the possibility that genotypes are involved in such differences. After a two-week base-line period, 12 pairs of young adult male monozygotic twins were overfed by 4.2 MJ (1000 kcal) per day, 6 days a week, for a total of 84 days during a 100-day period. The total excess amount each man consumed was 353 MJ (84,000 kcal). During overfeeding, individual changes in body composition and topography of fat deposition varied considerably. The mean weight gain was 8.1 kg, but the range was 4.3 to 13.3 kg. The similarity within each pair in the response to overfeeding was significant (P less than 0.05) with respect to body weight, percentage of fat, fat mass, and estimated subcutaneous fat, with about three times more variance among pairs than within pairs (r approximately 0.5). After adjustment for the gains in fat mass, the within-pair similarity was particularly evident with respect to the changes in regional fat distribution and amount of abdominal visceral fat (P less than 0.01), with about six times as much variance among pairs as within pairs (r approximately 0.7). We conclude that the most likely explanation for the intrapair similarity in the adaptation to long-term overfeeding and for the variations in weight gain and fat distribution among the pairs of twins is that genetic factors are involved. These may govern the tendency to store energy as either fat or lean tissue and the various determinants of the resting expenditure of energy.

A consensus meeting was held in Bangkok, 21-23 May 2002, where experts and young scientists in the field of physical activity, energy expenditure and body-weight regulation discussed the different aspects of physical activity in relation to the emerging problem of obesity worldwide. The following consensus statement was accepted unanimously. 'The current physical activity guideline for adults of 30 minutes of moderate intensity activity daily, preferably all days of the week, is of importance for limiting health risks for a number of chronic diseases including coronary heart disease and diabetes. However for preventing weight gain or regain this guideline is likely to be insufficient for many individuals in the current environment. There is compelling evidence that prevention of weight regain in formerly obese individuals requires 60-90 minutes of moderate intensity activity or lesser amounts of vigorous intensity activity. Although definitive data are lacking, it seems likely that moderate intensity activity of approximately 45 to 60 minutes per day, or 1.7 PAL (Physical Activity Level) is required to prevent the transition to overweight or obesity. For children, even more activity time is recommended. A good approach for many individuals to obtain the recommended level of physical activity is to reduce sedentary behaviour by incorporating more incidental and leisure-time activity into the daily routine. Political action is imperative to effect physical and social environmental changes to enable and encourage physical activity. Settings in which these environmental changes can be implemented include the urban and transportation infrastructure, schools, and workplaces.'