Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic nephropathy (DN) is the most common cause of renal failure in the western hemisphere. Epidemiological studies have suggested a genetic susceptibility for DN. Linkage analysis showed evidence for a locus on chromosome 18q22.3-q23 in Turkish families. We report the construction of a transcript map of the target region on chromosome 18q22.3-q23 and analysis of the candidate gene ZNF236. By using recent publications, human genome databases, and a multitude of available protein-predicting programs, we obtained a detailed map of this 4.7-Mb-spanning region. We sequenced ZNF236 in patients with diabetic nephropathy and diabetes without nephropathy, as well as in unaffected controls. We observed multiple splice forms in all individuals but no mutation in any of the patients. It seems improbable, therefore, that ZNF236 is a gene that confers DN susceptibility.
 ...
PMID:The Kruppel-like zinc-finger gene ZNF236 is alternatively spliced and excluded as susceptibility gene for diabetic nephropathy. 1290 66

There is increasing evidence that pleiotropy, the association of multiple traits with the same genetic variants/loci, is a very common phenomenon. Cross-phenotype association tests are often used to jointly analyze multiple traits from a genome-wide association study (GWAS). The underlying methods, however, are often designed to test the global null hypothesis that there is no association of a genetic variant with any of the traits, the rejection of which does not implicate pleiotropy. In this article, we propose a new statistical approach, PLACO, for specifically detecting pleiotropic loci between two traits by considering an underlying composite null hypothesis that a variant is associated with none or only one of the traits. We propose testing the null hypothesis based on the product of the Z-statistics of the genetic variants across two studies and derive a null distribution of the test statistic in the form of a mixture distribution that allows for fractions of variants to be associated with none or only one of the traits. We borrow approaches from the statistical literature on mediation analysis that allow asymptotic approximation of the null distribution avoiding estimation of nuisance parameters related to mixture proportions and variance components. Simulation studies demonstrate that the proposed method can maintain type I error and can achieve major power gain over alternative simpler methods that are typically used for testing pleiotropy. PLACO allows correlation in summary statistics between studies that may arise due to sharing of controls between disease traits. Application of PLACO to publicly available summary data from two large case-control GWAS of Type 2 Diabetes and of Prostate Cancer implicated a number of novel shared genetic regions: 3q23 (ZBTB38), 6q25.3 (RGS17), 9p22.1 (HAUS6), 9p13.3 (UBAP2), 11p11.2 (RAPSN), 14q12 (AKAP6), 15q15 (KNL1) and 18q23 (ZNF236).
 ...
PMID:A powerful method for pleiotropic analysis under composite null hypothesis identifies novel shared loci between Type 2 Diabetes and Prostate Cancer. 3329 Apr 8