title: Five linkage regions each harbor multiple type 2 diabetes genes in the African American subset of the GENNID Study.
abstract: We previously localized type 2 diabetes (T2D)-susceptibility genes to five chromosomal regions through a genome-wide linkage scan of T2D and age of diagnosis (AOD) in the African American subset of the GENNID sample. To follow up these findings, we repeated the linkage and association analysis using genotypes on an additional 9203 fine-mapping single nucleotide polymorphisms (SNPs) selected to tag genes under the linkage peaks. In each of the five regions, we confirmed linkage and inferred the presence of ≥2 susceptibility genes. The evidence of multiple susceptibility genes consisted of: (1) multiple linkage peaks in four of the five regions; and (2) association of T2D and AOD with SNPs within ≥2 genes in every region. The associated genes included 3 previously reported to associate with T2D or related traits (GRB10, NEDD4L, LIPG) and 24 novel candidate genes, including genes in lipid metabolism (ACOXL) and cell-cell and cell-matrix adhesion (MAGI2, CLDN4, CTNNA2).
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112 5330, USA. sandy@genetics.utah.edu
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hasstedt
authors.forename: Heather M
authors.initials: HM
authors.lastname: Highland
authors.forename: Steven C
authors.initials: SC
authors.lastname: Elbein
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hanis
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Das
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics; D021982:Cell-Matrix Junctions / Q000737:chemistry / Q000235:genetics; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D062506:Claudin-4 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D005260:Female; D051383:GRB10 Adaptor Protein / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D051528:Guanylate Kinases; D006801:Humans; D008049:Lipase / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult; D051178:alpha Catenin / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C568157:CLDN4 protein, human; C079671:CTNNA2 protein, human; D002352:Carrier Proteins; D062506:Claudin-4; D056827:Endosomal Sorting Complexes Required for Transport; C096358:GRB10 protein, human; D051178:alpha Catenin; D051383:GRB10 Adaptor Protein; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; C410382:LIPG protein, human; D008049:Lipase
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