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dc.contributor.authorLindström, Saraen_US
dc.contributor.authorAblorh, Akweleyen_US
dc.contributor.authorChapman, Braden_US
dc.contributor.authorGusev, Alexanderen_US
dc.contributor.authorChen, Garyen_US
dc.contributor.authorTurman, Constanceen_US
dc.contributor.authorEliassen, A. Heatheren_US
dc.contributor.authorPrice, Alkes L.en_US
dc.contributor.authorHenderson, Brian E.en_US
dc.contributor.authorLe Marchand, Loicen_US
dc.contributor.authorHofmann, Oliveren_US
dc.contributor.authorHaiman, Christopher A.en_US
dc.contributor.authorKraft, Peteren_US
dc.date.accessioned2016-12-02T15:26:21Z
dc.date.issued2016en_US
dc.identifier.citationLindström, S., A. Ablorh, B. Chapman, A. Gusev, G. Chen, C. Turman, A. H. Eliassen, et al. 2016. “Deep targeted sequencing of 12 breast cancer susceptibility regions in 4611 women across four different ethnicities.” Breast Cancer Research : BCR 18 (1): 109. doi:10.1186/s13058-016-0772-7. http://dx.doi.org/10.1186/s13058-016-0772-7.en
dc.identifier.issn1465-5411en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29626222
dc.description.abstractBackground: Although genome-wide association studies (GWASs) have identified thousands of disease susceptibility regions, the underlying causal mechanism in these regions is not fully known. It is likely that the GWAS signal originates from one or many as yet unidentified causal variants. Methods: Using next-generation sequencing, we characterized 12 breast cancer susceptibility regions identified by GWASs in 2288 breast cancer cases and 2323 controls across four populations of African American, European, Japanese, and Hispanic ancestry. Results: After genotype calling and quality control, we identified 137,530 single-nucleotide variants (SNVs); of those, 87.2 % had a minor allele frequency (MAF) <0.005. For SNVs with MAF >0.005, we calculated the smallest number of SNVs needed to obtain a posterior probability set (PPS) such that there is 90 % probability that the causal SNV is included. We found that the PPS for two regions, 2q35 and 11q13, contained less than 5 % of the original SNVs, dramatically decreasing the number of potentially causal SNVs. However, we did not find strong evidence supporting a causal role for any individual SNV. In addition, there were no significant gene-based rare SNV associations after correcting for multiple testing. Conclusions: This study illustrates some of the challenges faced in fine-mapping studies in the post-GWAS era, most importantly the large sample sizes needed to identify rare-variant associations or to distinguish the effects of strongly correlated common SNVs. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0772-7) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s13058-016-0772-7en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097387/pdf/en
dash.licenseLAAen_US
dc.subjectBreast canceren
dc.subjectFine-mappingen
dc.subjectNext-generation sequencingen
dc.subjectMultiethnic analysisen
dc.subjectGWASen
dc.titleDeep targeted sequencing of 12 breast cancer susceptibility regions in 4611 women across four different ethnicitiesen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBreast Cancer Research : BCRen
dash.depositing.authorAblorh, Akweleyen_US
dc.date.available2016-12-02T15:26:21Z
dc.identifier.doi10.1186/s13058-016-0772-7*
dash.authorsorderedfalse
dash.identifier.orcid0000-0002-9531-3856en_US
dash.contributor.affiliatedAblorh, Akweley
dash.contributor.affiliatedPrice, Alkes
dash.contributor.affiliatedTurman, Constance
dash.contributor.affiliatedEliassen, A.
dash.contributor.affiliatedChapman, Brad
dash.contributor.affiliatedGusev, Alexander
dash.contributor.affiliatedKraft, Phillip
dc.identifier.orcid0000-0002-9531-3856


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