A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma.
To identify a gene(s) susceptible to nasopharyngeal carcinoma (NPC), we carried out a genome-wide association study (GWAS) through genotyping of more than 500,000 tag single-nucleotide polymorphisms (SNPs), using an initial sample set of 111 unrelated NPC patients and 260 controls of a Malaysian Chinese population. We further evaluated the top 200 SNPs showing the smallest P-values, using a replication sample set that consisted of 168 cases and 252 controls. The combined analysis of the two sets of samples found an SNP in intron 3 of the ITGA9 (integrin-alpha 9) gene, rs2212020, to be strongly associated with NPC (P=8.27 x 10(-7), odds ratio (OR)=2.24, 95% confidence intervals (CI)=1.59-3.15). The gene is located at 3p21 which is commonly deleted in NPC cells. We subsequently genotyped additional 19 tag SNPs within a 40-kb linkage disequilibrium (LD) block surrounding this landmark SNP. Among them, SNP rs189897 showed the strongest association with a P-value of 6.85 x 10(-8) (OR=3.18, 95% CI=1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population.
Ng
Ching Ching
CC
Laboratory for International Alliance, RIKEN Center for Genomic Medicine, Tsurumi-ku, Yokohama, Japan. ccng@um.edu.my
Yew
Poh Yin
PY
Puah
Suat Moi
SM
Krishnan
Gopala
G
Yap
Lee Fah
LF
Teo
Soo Hwang
SH
Lim
Paul Vey Hong
PV
Govindaraju
Selvaratnam
S
Ratnavelu
Kananathan
K
Sam
Choon Kook
CK
Takahashi
Atsushi
A
Kubo
Michiaki
M
Kamatani
Naoyuki
N
Nakamura
Yusuke
Y
Mushiroda
Taisei
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016023:Integrins / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D055815:Young Adult
C541973:ITGA9 protein, human; D016023:Integrins