title: Analysis of candidate genes on chromosome 20q12-13.1 reveals evidence for BMI mediated association of PREX1 with type 2 diabetes in European Americans.
abstract: Chromosome 20q12-q13.1 has been linked to type 2 diabetes (T2D) in multiple populations. We examined the influence of genes in this region on T2D and BMI in two European American case-control populations. SNPs were genotyped in 300 diabetic patients and 310 controls. A subset of 72 SNPs were further genotyped in 470 cases and 442 controls. All genes examined showed evidence of association with T2D in the initial sample (additive P-value [P(a)]=0.00090-0.045). SNPs near PREX1 were also associated in the second case-control population (P(a)=0.017-0.042). The combined analysis resulted in the same SNPs, among others, associated with T2D (P(a)=0.0013-0.041). Stratification analysis by T2D status showed that association with BMI was observed solely in cases (P(a)=0.0018-0.041). Mediation testing revealed that 30-40% of the effects of these SNPs on T2D were significantly mediated by BMI. SNPs near PREX1 may contribute to T2D susceptibility mediated through effects of adiposity in European Americans.
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Lewis
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Ellington
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Lingyi
authors.initials: L
authors.lastname: Lu
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000569:Americas; D015992:Body Mass Index; D016022:Case-Control Studies; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C453280:PREX1 protein, human