A genome-wide scan for breast cancer risk haplotypes among African American women.

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...

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Main Authors: 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 Berg, Loic Le Marchand, Laurence N Kolonel, Brian E Henderson, Chris A Haiman, Daniel O Stram
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0057298&type=printable
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author 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 Berg
Loic Le Marchand
Laurence N Kolonel
Brian E Henderson
Chris A Haiman
Daniel O Stram
author_facet 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 Berg
Loic Le Marchand
Laurence N Kolonel
Brian E Henderson
Chris A Haiman
Daniel O Stram
author_sort Chi Song
collection DOAJ
description 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.
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spelling doaj-art-e998d726caf54b709e7bda85044923062025-08-20T03:25:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5729810.1371/journal.pone.0057298A genome-wide scan for breast cancer risk haplotypes among African American women.Chi SongGary K ChenRobert C MillikanChristine B AmbrosoneEsther M JohnLeslie BernsteinWei ZhengJennifer J HuRegina G ZieglerSarah NyanteElisa V BanderaSue A InglesMichael F PressSandra L DemingJorge L Rodriguez-GilStephen J ChanockPeggy WanXin ShengLoreall C PoolerDavid J Van Den BergLoic Le MarchandLaurence N KolonelBrian E HendersonChris A HaimanDaniel O StramGenome-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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0057298&type=printable
spellingShingle 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 Berg
Loic Le Marchand
Laurence N Kolonel
Brian E Henderson
Chris A Haiman
Daniel O Stram
A genome-wide scan for breast cancer risk haplotypes among African American women.
PLoS ONE
title A genome-wide scan for breast cancer risk haplotypes among African American women.
title_full A genome-wide scan for breast cancer risk haplotypes among African American women.
title_fullStr A genome-wide scan for breast cancer risk haplotypes among African American women.
title_full_unstemmed A genome-wide scan for breast cancer risk haplotypes among African American women.
title_short A genome-wide scan for breast cancer risk haplotypes among African American women.
title_sort genome wide scan for breast cancer risk haplotypes among african american women
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0057298&type=printable
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