Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness

Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.     

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.     

A global synthesis reveals biodiversity loss as a major driver of ecosystem change

Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth's ecosystems. Further species loss will accelerate change in ecosystem processes, but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition--two processes important in all ecosystems--are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21-40%) reduced plant production by 5-10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41-60%) had effects rivalling those of ozone, acidification, elevated CO(2) and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO(2) and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts.