A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma

Ching Ching Ng, Poh Yin Yew, Suat Moi Puah, Gopala Krishnan, Lee Fah Yap, Soo Hwang Teo, Paul Vey Hong Lim, Selvaratnam Govindaraju, Kananathan Ratnavelu, Choon Kook Sam, Atsushi Takahashi, Michiaki Kubo, Naoyuki Kamatani, Yusuke Nakamura, Taisei Mushiroda

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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-α 9) gene, rs2212020, to be strongly associated with NPC (P8.27 × 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 × 10 8 (OR3.18, 95% CI1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population.

Original languageEnglish
Pages (from-to)392-397
Number of pages6
JournalJournal of Human Genetics
Volume54
Issue number7
DOIs
Publication statusPublished - 01-07-2009

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Genome-Wide Association Study
Single Nucleotide Polymorphism
Genes
Linkage Disequilibrium
Integrins
Introns
Population
Nasopharyngeal carcinoma
Odds Ratio
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Ng, C. C., Yew, P. Y., Puah, S. M., Krishnan, G., Yap, L. F., Teo, S. H., ... Mushiroda, T. (2009). A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma. Journal of Human Genetics, 54(7), 392-397. https://doi.org/10.1038/jhg.2009.49
Ng, Ching Ching ; Yew, Poh Yin ; Puah, Suat Moi ; Krishnan, Gopala ; Yap, Lee Fah ; Teo, Soo Hwang ; Lim, Paul Vey Hong ; Govindaraju, Selvaratnam ; Ratnavelu, Kananathan ; Sam, Choon Kook ; Takahashi, Atsushi ; Kubo, Michiaki ; Kamatani, Naoyuki ; Nakamura, Yusuke ; Mushiroda, Taisei. / A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma. In: Journal of Human Genetics. 2009 ; Vol. 54, No. 7. pp. 392-397.
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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-α 9) gene, rs2212020, to be strongly associated with NPC (P8.27 × 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 × 10 8 (OR3.18, 95{\%} CI1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population.",
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Ng, CC, Yew, PY, Puah, SM, Krishnan, G, Yap, LF, Teo, SH, Lim, PVH, Govindaraju, S, Ratnavelu, K, Sam, CK, Takahashi, A, Kubo, M, Kamatani, N, Nakamura, Y & Mushiroda, T 2009, 'A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma', Journal of Human Genetics, vol. 54, no. 7, pp. 392-397. https://doi.org/10.1038/jhg.2009.49

A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma. / Ng, Ching Ching; Yew, Poh Yin; Puah, Suat Moi; Krishnan, Gopala; Yap, Lee Fah; Teo, Soo Hwang; Lim, Paul Vey Hong; Govindaraju, Selvaratnam; Ratnavelu, Kananathan; Sam, Choon Kook; Takahashi, Atsushi; Kubo, Michiaki; Kamatani, Naoyuki; Nakamura, Yusuke; Mushiroda, Taisei.

In: Journal of Human Genetics, Vol. 54, No. 7, 01.07.2009, p. 392-397.

Research output: Contribution to journalArticle

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AU - Ng, Ching Ching

AU - Yew, Poh Yin

AU - Puah, Suat Moi

AU - Krishnan, Gopala

AU - Yap, Lee Fah

AU - Teo, Soo Hwang

AU - Lim, Paul Vey Hong

AU - Govindaraju, Selvaratnam

AU - Ratnavelu, Kananathan

AU - Sam, Choon Kook

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Mushiroda, Taisei

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