Circulating glucose levels are tightly regulated. To identify novel glycemic loci, we performed meta-analyses of 21 genome-wide associations studies informative for fasting glucose (FG), fasting insulin (FI) and indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 non-diabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with FG/HOMA-B and two associated with FI/HOMA-IR. These include nine new FG loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and FAM148B) and one influencing FI/HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB/TMEM195 with type 2 diabetes (T2D). Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify T2D risk loci, as well as loci that elevate FG modestly, but do not cause overt diabetes.

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction, but contributed little to our understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways may be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and genetic variants. We applied a novel joint meta-analytical approach to test associations with fasting insulin (FI) and glucose (FG) on a genome-wide scale. We present six previously unknown FI loci at P<5×10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496non-diabetic individuals. Risk variants were associated with higher triglyceride and lower HDL cholesterol levels, suggestive of a role for these FI loci in insulin resistance pathways. The localization of these additional loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

The aim of this study was to test the hypothesis that individual differences in the response of maximal O(2) uptake (VO(2max)) to a standardized training program are characterized by familial aggregation. A total of 481 sedentary adult Caucasians from 98 two-generation families was exercise trained for 20 wk and was tested for VO(2max) on a cycle ergometer twice before and twice after the training program. The mean increase in VO(2max) reached approximately 400 ml/min, but there was considerable heterogeneity in responsiveness, with some individuals experiencing little or no gain, whereas others gained >1.0 l/min. An ANOVA revealed that there was 2.5 times more variance between families than within families in the VO(2max) response variance. With the use of a model-fitting procedure, the most parsimonious models yielded a maximal heritability estimate of 47% for the VO(2max) response, which was adjusted for age and sex with a maternal transmission of 28% in one of the models. We conclude that the trainability of VO(2max) is highly familial and includes a significant genetic component.

The effects of silicon application on the drought tolerance of sorghum (Sorghum bicolor (L.) Moench) were investigated for two cultivars differing in drought susceptibility. Silicon application ameliorated the decrease in dry weight under drought stress conditions, but had no effect on dry matter production under wet conditions. Under dry conditions, silicon‐applied sorghum had a lower shoot to root (S/R) ratio, indicating the facilitation of root growth and the maintenance of the photosynthetic rate and stomatal conductance at a higher level compared with plants grown without silicon application. The diurnal determination of the transpiration rate indicated that the silicon‐applied sorghum could extract a larger amount of water from drier soil and maintain a higher stomatal conductance. Very similar effects of silicon application were observed for both cultivars regardless of their drought susceptibility. These results suggest that silicon application may be useful to improve the drought tolerance of sorghum via the enhancement of water uptake ability.