A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Prognostic value of DLGAP5 in colorectal cancer

DLG7 (disc large homolog 7) is a microtubule-associated protein encoded by DLGAP5 (DLG associated protein 5) gene and has an important role during spindle assembly. Spindle assembly deregulation is a well-known cause of genomic instability. The aim of this study was to investigate the influence of DLGAP5 expression on survival and to evaluate its potential use as a biomarker in colorectal cancer (CRC).DLGAP5 expression was measured in the primary tumor and corresponding normal mucosa samples from 109 patients with CRC and correlated to clinical and pathological data. The results were validated in a second, publically available patient cohort. Molecular effects of DLG7/DLGAP5 in CRC were analyzed via functional assays in knockdown cell lines.DLGAP5 downregulation led to a significant reduction of the invasion and migration potential in CRC. In addition, DLGAP5 expression correlates with nodal status and advanced UICC stage (III-IV).Subgroup analyses revealed a correlation between DLGAP5 overexpression and poor survival in patients with non-metastatic disease (M0). Furthermore, overexpression of DLGAP5 is associated with worse overall survival in distinct molecular CRC subtypes.The results of this study suggest the importance of DLGAP5 in defining a more aggressive CRC phenotype. DLG7/DLGAP5 represents a potential biomarker for CRC in molecular subgroups of CRC

Migration, Ethnonationalist Destinations and Social Divisions: Non-Jewish Immigrants in Israel

Immigrants in ethno-nationalist destinations encounter difficulties of integration particularly to the extent that they lack shared ethnicity with natives. But an analysis of non-Jewish immigrants in Israel shows that lacking shared ethnicity is by no means an insurmountable obstacle to integration, even in strongly ethno-nationalist destinations. Non-Jewish immigrants – even those who entered as migrant workers – have achieved a certain degree of membership in Israeli society. Moreover, their presence has exacerbated certain divisions among Jewish Israelis. Even in ethno-nationalist destinations, then, the immigration of non-co-ethnics does not result only/inevitably in divisions between immigrants and natives: it can also divide natives, while some immigrants and natives find a measure of common ground