The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

New advances in understanding sensitive periods in brain development

Is a dog ever too old to learn new tricks? We review recent findings on sensitive periods in brain development, ranging from sensory processing to high-level cognitive abilities in humans. We conclude that there are multiple varieties of, and mechanisms underlying, these changes. However, many sensitive periods may be a consequence of the basic processes underlying postnatal functional brain development

Accumulating brisk walking for fitness, cardiovascular risk and psychological health

MURPHY, M., A. NEVILL, C. NEVILLE, S. BIDDLE, and A. HARDMAN. Accumulating brisk walking for fitness, cardiovascular risk, and psychological health. Med. Sci. Sports Exerc., Vol. 34, No. 9, pp. 1468–1474, 2002. Purpose: To compare the effects of different patterns of regular brisk walking on fitness, risk factors for cardiovascular disease, and psychological well-being in previously sedentary adults. Methods: Twenty-one subjects (14 women), aged 44.5 ± 6.1 yr (mean ± SD) were randomly assigned to two different, 6-wk programs of brisk walking in a cross-over design, with an interval of 2 wk. One program comprised one 30-min walk per day, 5 d·wk-1 (long bout) and the other three 10-min walks per day, also 5 d·wk-1 (short bouts). All walking was at 70–80% of predicted maximal heart rate. Maximal oxygen uptake ([latin capital V with dot above]O2max), body composition, resting arterial blood pressure, fasting plasma lipoprotein variables, and psychological parameters were assessed before and after each program. Results: Overall, subjects completed 88.2 ± 1.1% and 91.3 ± 4.1% of prescribed total walking time in the short- and long-bout programs, respectively. Both programs increased plasma concentrations of high-density lipoprotein cholesterol, and decreased concentrations of triacylglycerol and total cholesterol (all P < 0.05). There were no changes in body mass, but the sum of four skinfolds, waist circumference, and hip circumference were decreased after both walking programs (all P < 0.05). Predicted [latin capital V with dot above]O2max increased with both programs (P < 0.05), but this increase was greater with the program based on short bouts (P < 0.05). Both walking patterns resulted in similar decreases in tension/anxiety (P < 0.05). Conclusion: These findings suggest that three short bouts (10 min) of brisk walking accumulated throughout the day are at least as effective as one continuous bout of equal total duration in reducing cardiovascular risk and improving aspects of mood in previously sedentary individuals