Analysis of candidate genes on chromosome 20q12-13.1 reveals evidence for BMI mediated association of PREX1 with type 2 diabetes in European Americans.
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.
Lewis
Joshua P
JP
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Palmer
Nicholette D
ND
Ellington
Jennifer B
JB
Divers
Jasmin
J
Ng
Maggie C Y
MC
Lu
Lingyi
L
Langefeld
Carl D
CD
Freedman
Barry I
BI
Bowden
Donald W
DW
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*
D020662:Guanine Nucleotide Exchange Factors; C453280:PREX1 protein, human