No Robust Evidence of Future Changes in Major Stratospheric Sudden Warmings: A Multi-model Assessment from CCMI.

Major stratospheric sudden warmings (SSWs) are the largest instance of wintertime variability in the Arctic stratosphere. Due to their relevance for the troposphere-stratosphere system, several previous studies have focused on their potential response to anthropogenic forcings. However, a wide range of results have been reported, from a future increase in the frequency of SSWs to a decrease. Several factors might explain these contradictory results, notably the use of different metrics for the identification of SSWs, and the impact of large climatological biases in single-model studies. Here we revisit the question of future SSWs changes, using an identical set of metrics applied consistently across 12 different models participating in the Chemistry Climate Model Initiative. From analyzing future integrations we find no statistically significant change in the frequency of SSWs over the 21st century, irrespective of the metric used for the identification of SSWs. Changes in other SSWs characteristics, such as their duration and the tropospheric forcing, are also assessed: again, we find no evidence of future changes over the 21st century.

Genetic and functional assessment of the role of the rs13431652-A and rs573225-A alleles in the G6PC2 promoter that are strongly associated with elevated fasting glucose levels.

OBJECTIVE: Genome-wide association studies have identified a single nucleotide polymorphism (SNP), rs560887, located in a G6PC2 intron that is highly correlated with variations in fasting plasma glucose (FPG). G6PC2 encodes an islet-specific glucose-6-phosphatase catalytic subunit. This study examines the contribution of two G6PC2 promoter SNPs, rs13431652 and rs573225, to the association signal. RESEARCH DESIGN AND METHODS: We genotyped 9,532 normal FPG participants (FPG <6.1 mmol/l) for three G6PC2 SNPs, rs13431652 (distal promoter), rs573225 (proximal promoter), rs560887 (3rd intron). We used regression analyses adjusted for age, sex, and BMI to assess the association with FPG and haplotype analyses to assess comparative SNP contributions. Fusion gene and gel retardation analyses characterized the effect of rs13431652 and rs573225 on G6PC2 promoter activity and transcription factor binding. RESULTS: Genetic analyses provide evidence for a strong contribution of the promoter SNPs to FPG variability at the G6PC2 locus (rs13431652: ß = 0.075, P = 3.6 × 10(-35); rs573225 ß = 0.073 P = 3.6 × 10(-34)), in addition to rs560887 (ß = 0.071, P = 1.2 × 10(-31)). The rs13431652-A and rs573225-A alleles promote increased NF-Y and Foxa2 binding, respectively. The rs13431652-A allele is associated with increased FPG and elevated promoter activity, consistent with the function of G6PC2 in pancreatic islets. In contrast, the rs573225-A allele is associated with elevated FPG but reduced promoter activity. CONCLUSIONS: Genetic and in situ functional data support a potential role for rs13431652, but not rs573225, as a causative SNP linking G6PC2 to variations in FPG, though a causative role for rs573225 in vivo cannot be ruled out.