University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Clinical Pathology
  • Clinical Pathology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Clinical Pathology
  • Clinical Pathology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Deep targeted sequencing of 12 breast cancer susceptibility regions in 4611 women across four different ethnicities

    Thumbnail
    Download
    Published version (732.4Kb)

    Citations
    Scopus
    Web of Science
    Altmetric
    4
    2
    Author
    Lindstroem, S; Ablorh, A; Chapman, B; Gusev, A; Chen, G; Turman, C; Eliassen, AH; Price, AL; Henderson, BE; Le Marchand, L; ...
    Date
    2016-11-05
    Source Title
    Breast Cancer Research
    Publisher
    BMC
    University of Melbourne Author/s
    Hofmann, Oliver
    Affiliation
    Clinical Pathology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Lindstroem, S., Ablorh, A., Chapman, B., Gusev, A., Chen, G., Turman, C., Eliassen, A. H., Price, A. L., Henderson, B. E., Le Marchand, L., Hofmann, O., Haiman, C. A. & Kraft, P. (2016). Deep targeted sequencing of 12 breast cancer susceptibility regions in 4611 women across four different ethnicities. BREAST CANCER RESEARCH, 18 (1), https://doi.org/10.1186/s13058-016-0772-7.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254676
    DOI
    10.1186/s13058-016-0772-7
    Abstract
    BACKGROUND: 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.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Clinical Pathology - Research Publications [385]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors