title: A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma.
abstract: 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.
authors.affiliation: Laboratory for International Alliance, RIKEN Center for Genomic Medicine, Tsurumi-ku, Yokohama, Japan. ccng@um.edu.my
authors.forename: Ching Ching
authors.initials: CC
authors.lastname: Ng
authors.forename: Poh Yin
authors.initials: PY
authors.lastname: Yew
authors.forename: Suat Moi
authors.initials: SM
authors.lastname: Puah
authors.forename: Gopala
authors.initials: G
authors.lastname: Krishnan
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.forename: Soo Hwang
authors.initials: SH
authors.lastname: Teo
authors.forename: Paul Vey Hong
authors.initials: PV
authors.lastname: Lim
authors.forename: Selvaratnam
authors.initials: S
authors.lastname: Govindaraju
authors.forename: Kananathan
authors.initials: K
authors.lastname: Ratnavelu
authors.forename: Choon Kook
authors.initials: CK
authors.lastname: Sam
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
mesh_terms: 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
chemical_list: C541973:ITGA9 protein, human; D016023:Integrins