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 J. 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 journalArticlepeer-review

14 Scopus citations


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 (US)
Article numbere57298
JournalPloS one
Issue number2
StatePublished - Feb 28 2013

ASJC Scopus subject areas

  • General


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