A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women

Chi Song, Gary K. Chen, Robert C. Millikan, Christine B. Ambrosone, Esther M. John, Leslie Bernstein, Wei Zheng, Jennifer Hu, Regina G. Ziegler, Sarah Nyante, Elisa V. Bandera, Sue A. Ingles, Michael F. Press, Sandra L. Deming, Jorge L. Rodriguez-Gil, Stephen J. Chanock, Peggy Wan, Xin Sheng, Loreall C. Pooler, David J. Van Den BergLoic Le Marchand, Laurence N. Kolonel, Brian E. Henderson, Chris A. Haiman, Daniel O. Stram

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density.

Original languageEnglish
Article numbere57298
JournalPLoS One
Volume8
Issue number2
DOIs
StatePublished - Feb 28 2013

Fingerprint

African Americans
breast neoplasms
Haplotypes
haplotypes
Genes
Genome
Breast Neoplasms
genome
Chromosomes
Ports and harbors
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
chromosomes
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 4
loci
Chromosomes, Human, Pair 1
Genome-Wide Association Study

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Song, C., Chen, G. K., Millikan, R. C., Ambrosone, C. B., John, E. M., Bernstein, L., ... Stram, D. O. (2013). A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women. PLoS One, 8(2), [e57298]. https://doi.org/10.1371/journal.pone.0057298

A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women. / Song, Chi; Chen, Gary K.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Chanock, Stephen J.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Chris A.; Stram, Daniel O.

In: PLoS One, Vol. 8, No. 2, e57298, 28.02.2013.

Research output: Contribution to journalArticle

Song, C, Chen, GK, Millikan, RC, Ambrosone, CB, John, EM, Bernstein, L, Zheng, W, Hu, J, Ziegler, RG, Nyante, S, Bandera, EV, Ingles, SA, Press, MF, Deming, SL, Rodriguez-Gil, JL, Chanock, SJ, Wan, P, Sheng, X, Pooler, LC, Van Den Berg, DJ, Le Marchand, L, Kolonel, LN, Henderson, BE, Haiman, CA & Stram, DO 2013, 'A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women', PLoS One, vol. 8, no. 2, e57298. https://doi.org/10.1371/journal.pone.0057298
Song C, Chen GK, Millikan RC, Ambrosone CB, John EM, Bernstein L et al. A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women. PLoS One. 2013 Feb 28;8(2). e57298. https://doi.org/10.1371/journal.pone.0057298
Song, Chi ; Chen, Gary K. ; Millikan, Robert C. ; Ambrosone, Christine B. ; John, Esther M. ; Bernstein, Leslie ; Zheng, Wei ; Hu, Jennifer ; Ziegler, Regina G. ; Nyante, Sarah ; Bandera, Elisa V. ; Ingles, Sue A. ; Press, Michael F. ; Deming, Sandra L. ; Rodriguez-Gil, Jorge L. ; Chanock, Stephen J. ; Wan, Peggy ; Sheng, Xin ; Pooler, Loreall C. ; Van Den Berg, David J. ; Le Marchand, Loic ; Kolonel, Laurence N. ; Henderson, Brian E. ; Haiman, Chris A. ; Stram, Daniel O. / A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women. In: PLoS One. 2013 ; Vol. 8, No. 2.
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