New genetic loci link adipose and insulin biology to body fat distribution.

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, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display 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

New susceptibility loci associated with kidney disease in type 1 diabetes

WOS:000309817900008Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.Peer reviewe

Managed nutrient reduction impacts on nutrient concentrations, water clarity, primary production, and hypoxia in a north temperate estuary

Except for the Providence River and side embayments like Greenwich Bay, Narragansett Bay can no longer be considered eutrophic. In summer 2012 managed nitrogen treatment in Narragansett Bay achieved a goal of reducing effluent dissolved inorganic nitrogen inputs by over 50%. Narragansett Bay represents a small northeast US estuary that had been heavily loaded with sewage effluent nutrients since the late 1800s. The input reduction was reflected in standing stock nutrients resulting in a statistically significant 60% reduction in concentration. In the Providence River estuary, total nitrogen decreased from 100 μm to about 40 μm, for example. We tested four environmental changes that might be associated with the nitrogen reduction. System apparent production was significantly decreased by 31% and 45% in the upper and mid Bay. Nutrient reductions resulted in statistically improved water clarity in the mid and upper Bay and in a 34% reduction in summer hypoxia. Nitrogen reduction also reduced the winter spring diatom bloom; winter chlorophyll levels after nutrient reduction have been significantly lower than before the reduction. The impact on the Bay will continue to evolve over the next few years and be a natural experiment for other temperate estuaries that will be experiencing nitrogen reduction. To provide perspective we review factors effecting hypoxia in other estuaries with managed nutrient reduction and conclude that, as in Narragansett Bay, physical factors can be as important as nutrients. On a positive note managed nutrient reduction has mitigated further deterioration in most estuaries

Production patterns in Massachusetts Bay with outfall relocation

On September 6, 2000, the sewage outfall at the mouth of Boston Harbor was relocated 15 km offshore to alleviate pollution in Boston Harbor. The expected responses for nutrients and water column productivity parameters were for values to decrease at Boston Harbor, to increase at the outfall location, and to remain unchanged at the boundary of the near field region within 5 km of the outfall. Average values for water column measurements from 1992 to 2004 indicated these general responses with some exceptions. At the Harbor, nutrients decreased and chlorophyll increased but 14C primary productivity remained statistically unchanged. At the new outfall location and at the boundary of the near field, nutrients increased and chlorophyll increased but primary productivity remained unchanged. Physical factors affecting primary production, such as spring water temperature, stratification, and wind, had more affects on productivity patterns than nutrients from outfall relocation in the near field. A decrease in summer zooplankton after outfall relocation appeared to be due to a region-wide factor rather than outfall effluents. © 2007 Estuarine Research Federation