TY  - JOUR
A1  - Iyengar, Sudha K.
A1  - Sedor, John R.
A1  - Freedman, Barry I.
A1  - Kao, W. H. Linda
A1  - Kretzler, Matthias
A1  - Keller, Benjamin J.
A1  - Abboud, Hanna E.
A1  - Adler, Sharon G.
A1  - Best, Lyle G.
A1  - Bowden, Donald W.
A1  - Burlock, Allison
A1  - Chen, Yii-Der Ida
A1  - Cole, Shelley A.
A1  - Comeau, Mary E.
A1  - Curtis, Jeffrey M.
A1  - Divers, Jasmin
A1  - Drechsler, Christiane
A1  - Duggirala, Ravi
A1  - Elston, Robert C.
A1  - Guo, Xiuqing
A1  - Huang, Huateng
A1  - Hoffmann, Michael Marcus
A1  - Howard, Barbara V.
A1  - Ipp, Eli
A1  - Kimmel, Paul L.
A1  - Klag, Michael J.
A1  - Knowler, William C.
A1  - Kohn, Orly F.
A1  - Leak, Tennille S.
A1  - Leehey, David J.
A1  - Li, Man
A1  - Malhotra, Alka
A1  - März, Winfried
A1  - Nair, Viji
A1  - Nelson, Robert G.
A1  - Nicholas, Susanne B.
A1  - O’Brien, Stephen J.
A1  - Pahl, Madeleine V.
A1  - Parekh, Rulan S.
A1  - Pezzolesi, Marcus G.
A1  - Rasooly, Rebekah S.
A1  - Rotimi, Charles N.
A1  - Rotter, Jerome I.
A1  - Schelling, Jeffrey R.
A1  - Seldin, Michael F.
A1  - Shah, Vallabh O.
A1  - Smiles, Adam M.
A1  - Smith, Michael W.
A1  - Taylor, Kent D.
A1  - Thameem, Farook
A1  - Thornley-Brown, Denyse P.
A1  - Truitt, Barbara J.
A1  - Wanner, Christoph
A1  - Weil, E. Jennifer
A1  - Winkler, Cheryl A.
A1  - Zager, Philip G.
A1  - Igo, Jr, Robert P.
A1  - Hanson, Robert L.
A1  - Langefeld, Carl D.
T1  - Genome-wide association and trans-ethnic meta-analysis for advanced diabetic kidney disease: Family Investigation of Nephropathy and Diabetes (FIND)
JF  - PLoS Genetics
N2  - Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10\(^{−9}\)). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10\(^{−8}\)), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.
KW  - diabetic kidney disease
KW  - genome-wide association study
KW  - Family Investigation of Nephropathy and Diabetes
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180545
VL  - 11
IS  - 8
ER  - 
TY  - JOUR
A1  - Gökbuget, N.
A1  - Kelsh, M.
A1  - Chia, V.
A1  - Advani, A.
A1  - Bassan, R.
A1  - Dombret, H.
A1  - Doubek, M.
A1  - Fielding, A. K.
A1  - Giebel, S.
A1  - Haddad, V.
A1  - Hoelzer, D.
A1  - Holland, C.
A1  - Ifrah, N.
A1  - Katz, A.
A1  - Maniar, T.
A1  - Martinelli, G.
A1  - Morgades, M.
A1  - O'Brien, S.
A1  - Ribera, J.-M.
A1  - Rowe, J. M.
A1  - Stein, A.
A1  - Topp, M.
A1  - Wadleigh, M.
A1  - Kantarjian, H.
T1  - Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia
JF  - Blood Cancer Journal
N2  - We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20–27%) and a median OS of 3.3 months (95% CI: 2.8–3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36–50%) and a median OS of 6.1 months (95% CI: 4.2–7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67–4.31) and improved OS (HR=0.536, 95% CI: 0.394–0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.
KW  - Acute lymphocytic leukaemia
KW  - Drug development
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164495
VL  - 6
ER  -