TY  - JOUR
A1  - Müller, Stefanie H.
A1  - Girard, Simon L.
A1  - Hopfner, Franziska
A1  - Merner, Nancy D.
A1  - Bourassa, Cynthia V.
A1  - Lorenz, Delia
A1  - Clark, Lorraine N.
A1  - Tittmann, Lukas
A1  - Soto-Ortolaza, Alexandra I.
A1  - Klebe, Stephan
A1  - Hallett, Mark
A1  - Schneider, Susanne A.
A1  - Hodgkinson, Colin A.
A1  - Lieb, Wolfgang
A1  - Wszolek, Zbigniew K.
A1  - Pendziwiat, Manuela
A1  - Lorenzo-Betancor, Oswaldo
A1  - Poewe, Werner
A1  - Ortega-Cubero, Sara
A1  - Seppi, Klaus
A1  - Rajput, Alex
A1  - Hussl, Anna
A1  - Rajput, Ali H.
A1  - Berg, Daniela
A1  - Dion, Patrick A.
A1  - Wurster, Isabel
A1  - Shulman, Joshua M.
A1  - Srulijes, Karin
A1  - Haubenberger, Dietrich
A1  - Pastor, Pau
A1  - Vilariño-Güell, Carles
A1  - Postuma, Ronald B.
A1  - Bernard, Geneviève
A1  - Ladwig, Karl-Heinz
A1  - Dupré, Nicolas
A1  - Jankovic, Joseph
A1  - Strauch, Konstantin
A1  - Panisset, Michel
A1  - Winkelmann, Juliane
A1  - Testa, Claudia M.
A1  - Reischl, Eva
A1  - Zeuner, Kirsten E.
A1  - Ross, Owen A.
A1  - Arzberger, Thomas
A1  - Chouinard, Sylvain
A1  - Deuschl, Günther
A1  - Louis, Elan D.
A1  - Kuhlenbäumer, Gregor
A1  - Rouleau, Guy A.
T1  - Genome-wide association study in essential tremor identifies three new loci
JF  - Brain
N2  - We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.
KW  - quality-control
KW  - disease
KW  - tool
KW  - movement disorders
KW  - genome-wide association study
KW  - tremor
KW  - genetics
KW  - essential tremor
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186541
VL  - 139
ER  - 
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  -