Strong association of common variants in the CDKN2A/CDKN2B region with type 2 diabetes in French Europids.
OBJECTIVE
Genome-wide association studies (GWASs) recently identified common variants in the CDKN2A/CDKN2B region on chromosome 9p as being strongly associated with type 2 diabetes. Since these association signals were not picked up by the French-Canadian GWAS, we sought to replicate these findings in the French Europid population and to further characterise the susceptibility variants at this novel locus.


METHODS
We genotyped 20 single nucleotide polymorphisms (SNPs) spanning the CDKN2A/CDKN2B locus in our type 2 diabetes case-control cohort. The association between CDKN2A/CDKN2B SNPs and quantitative metabolic traits was also examined in the normoglycaemic participants comprising the control cohort.


RESULTS
We report replication of the strong association of rs10811661 with type 2 diabetes found in the GWASs (P= 3.8 X 10(-7); OR 1.43 [95% CI 1.24-1.64]). The other CDKN2A/CDKN2B susceptibility variant, rs564398, did not attain statistical significance (p = 0.053; OR 1.11 [95% CI 1.00-1.24]) in the present study. We also obtained several additional nominal association signals (p < 0.05) at the CDKN2A/CDKN2B locus; however, only the rs3218018 result (p = 0.002) survived Bonferroni correction for multiple testing (adjusted p = 0.04).


CONCLUSIONS
Our comprehensive association study of common variation spanning the CDKN2A/CDKN2B locus confirms the strong association between the distal susceptibility variant rs10811661 and type 2 diabetes in the French population. Further genetic and functional studies are required to identify the aetiological variants at this locus and determine the cellular and physiological mechanisms by which they act to modulate type 2 diabetes susceptibility.
Duesing
K
K
Genomic Medicine, Imperial College London, Hammersmith Campus, Du Cane Rd, London, W12 0NN, UK.
Fatemifar
G
G
Charpentier
G
G
Marre
M
M
Tichet
J
J
Hercberg
S
S
Balkau
B
B
Froguel
P
P
Gibson
F
F
D020121:5' Untranslated Regions / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005602:France; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
D020121:5' Untranslated Regions; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16