Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population.
BACKGROUND
Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between D15S118 and D15S117 in a Japanese population using a region-wide case-control association test.


METHODS
A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed.


RESULTS
SNP2140 (rs2412747) (C/T) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal p value (p = 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07-1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing.


CONCLUSIONS
The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.
Yamaguchi
Yuka
Y
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. yama@genome.tokushima-u.ac.jp
Moritani
Maki
M
Tanahashi
Toshihito
T
Osabe
Dai
D
Nomura
Kyoko
K
Fujita
Yuka
Y
Keshavarz
Parvaneh
P
Kunika
Kiyoshi
K
Nakamura
Naoto
N
Yoshikawa
Toshikazu
T
Ichiishi
Eiichiro
E
Shiota
Hiroshi
H
Yasui
Natsuo
N
Inoue
Hiroshi
H
Itakura
Mitsuo
M
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide