Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Spatial-temporal succession of the vegetation in Xishuangbanna, China during 1976-2010: A case study based on RS technology and implications for eco-restoration

The spatial-temporal succession of regional vegetation in Xishuangbanna, China from 1976 to 2010 was studied based on RS technology. The results showed the area fluctuation of main vegetation types in the study area during the research period. There was no great change in the total area of main vegetation, with the fluctuation area ranging from 12,579.84 to 14,698.75 km(2), averaging 13,664.48 km(2) annually, and with the fluctuation ratio between -7.94% and 7.57%. The area of natural vegetation (tropical rainforest, tropical seasonal moist forest, tropical seasonal rainforest, and tropical mountainous evergreen broad-leaved forests) increased at first and gradually decreased afterwards, and the ratio of its distribution area to the total area of main vegetation was featured with an annual decrease, especially in 2005 and 2010. Both the distribution area and ratio of artificial vegetation (Rubber plantation) to the total area of main vegetation were characterized with the tendency of a gradual increase, especially in 2005 and 2010. Thus, the establishment of artificial vegetation (Rubber plantation) not only led to the decrease in natural vegetation (3641.16 km(2)) but also covered 343.66 km(2) of lands for other uses. The results also showed the distribution succession of main vegetation types in the study area during the research period. In the later research period (after 1999), compared with the early research period (before 1999), the distribution range of natural vegetation was characterized with a certain decrease in the following aspects as at different altitudes (1400m), and on different slopes (0-5 degrees, 5-8 degrees, 8-15 degrees, 15-25 degrees, 25-35 degrees, and >35 degrees). By contrast, the artificial vegetation was just the opposite whose distribution range was characterized with a tendency of a rapid growth at different altitudes, and on different slopes. It indicated that the establishment of artificial vegetation had broken the original ecological pattern in Xishuangbanna, which would bring direct threats to the regional ecological security and environment healthy development, thus countermeasures were urgent to be taken in order to prevent it from worsening. (C) 2014 Elsevier B.V. All rights reserved.The spatial-temporal succession of regional vegetation in Xishuangbanna, China from 1976 to 2010 was studied based on RS technology. The results showed the area fluctuation of main vegetation types in the study area during the research period. There was no great change in the total area of main vegetation, with the fluctuation area ranging from 12,579.84 to 14,698.75 km(2), averaging 13,664.48 km(2) annually, and with the fluctuation ratio between -7.94% and 7.57%. The area of natural vegetation (tropical rainforest, tropical seasonal moist forest, tropical seasonal rainforest, and tropical mountainous evergreen broad-leaved forests) increased at first and gradually decreased afterwards, and the ratio of its distribution area to the total area of main vegetation was featured with an annual decrease, especially in 2005 and 2010. Both the distribution area and ratio of artificial vegetation (Rubber plantation) to the total area of main vegetation were characterized with the tendency of a gradual increase, especially in 2005 and 2010. Thus, the establishment of artificial vegetation (Rubber plantation) not only led to the decrease in natural vegetation (3641.16 km(2)) but also covered 343.66 km(2) of lands for other uses. The results also showed the distribution succession of main vegetation types in the study area during the research period. In the later research period (after 1999), compared with the early research period (before 1999), the distribution range of natural vegetation was characterized with a certain decrease in the following aspects as at different altitudes (1400m), and on different slopes (0-5 degrees, 5-8 degrees, 8-15 degrees, 15-25 degrees, 25-35 degrees, and >35 degrees). By contrast, the artificial vegetation was just the opposite whose distribution range was characterized with a tendency of a rapid growth at different altitudes, and on different slopes. It indicated that the establishment of artificial vegetation had broken the original ecological pattern in Xishuangbanna, which would bring direct threats to the regional ecological security and environment healthy development, thus countermeasures were urgent to be taken in order to prevent it from worsening. (C) 2014 Elsevier B.V. All rights reserved