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Research article
Deke Jiang
Southern Medical University Nanfang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7888-2344
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background : Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis.Methods: We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls.Results: The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene set for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses are successfully replicated in the independent sample. Conclusions: This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risk. More experiments or larger samples are needed to validate their contribution to the pathogenic mechanism of HCC.
Keywords
knowledge-based genetic association; susceptibility; hepatitis B virus; hepatocellular carcinoma
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CURRENT STATUS: Published
View the published article at BMC Cancer.
No community comments so far
Editorial decision: Accept
On 07 Apr, 2020
Submission checks complete
On 04 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 28 Mar, 2020
Review #1 received
Received 27 Mar, 2020
Reviewer #1 agreed
On 13 Mar, 2020
Reviewers invited
Invitations sent on 13 Mar, 2020
Editor assigned
On 12 Mar, 2020
Submission checks complete
On 11 Mar, 2020
Editor invited
On 11 Mar, 2020
Version 2
Posted 10 Dec, 2019
No comments provided
Editorial decision: Major revision
On 17 Feb, 2020
Review #2 received
Received 07 Jan, 2020
Reviewer #2 agreed
On 03 Jan, 2020
Review #1 received
Received 09 Dec, 2019
Reviewers invited
Invitations sent on 03 Dec, 2019
Reviewer #1 agreed
On 03 Dec, 2019
Editor assigned
On 02 Dec, 2019
Submission checks complete
On 01 Dec, 2019
Editor invited
On 01 Dec, 2019
No comments provided
Editorial decision: Major revision
On 08 Oct, 2019
Review #2 received
Received 03 Oct, 2019
Review #1 received
Received 03 Oct, 2019
Reviewer #1 agreed
On 23 Sep, 2019
Reviewer #2 agreed
On 23 Sep, 2019
Reviewers invited
Invitations sent on 20 Sep, 2019
Editor assigned
On 15 Sep, 2019
Submission checks complete
On 11 Sep, 2019
Editor invited
On 11 Sep, 2019
First submitted
On 31 Aug, 2019
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A new preprint design is coming!
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See the published version of this preprint at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Deke Jiang
Southern Medical University Nanfang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7888-2344
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cancer.
No community comments so far
Editorial decision: Accept
On 07 Apr, 2020
Submission checks complete
On 04 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 28 Mar, 2020
Review #1 received
Received 27 Mar, 2020
Reviewer #1 agreed
On 13 Mar, 2020
Reviewers invited
Invitations sent on 13 Mar, 2020
Editor assigned
On 12 Mar, 2020
Submission checks complete
On 11 Mar, 2020
Editor invited
On 11 Mar, 2020
Version 2
Posted 10 Dec, 2019
No comments provided
Editorial decision: Major revision
On 17 Feb, 2020
Review #2 received
Received 07 Jan, 2020
Reviewer #2 agreed
On 03 Jan, 2020
Review #1 received
Received 09 Dec, 2019
Reviewers invited
Invitations sent on 03 Dec, 2019
Reviewer #1 agreed
On 03 Dec, 2019
Editor assigned
On 02 Dec, 2019
Submission checks complete
On 01 Dec, 2019
Editor invited
On 01 Dec, 2019
No comments provided
Editorial decision: Major revision
On 08 Oct, 2019
Review #2 received
Received 03 Oct, 2019
Review #1 received
Received 03 Oct, 2019
Reviewer #1 agreed
On 23 Sep, 2019
Reviewer #2 agreed
On 23 Sep, 2019
Reviewers invited
Invitations sent on 20 Sep, 2019
Editor assigned
On 15 Sep, 2019
Submission checks complete
On 11 Sep, 2019
Editor invited
On 11 Sep, 2019
First submitted
On 31 Aug, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
Background : Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis.Methods: We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls.Results: The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene set for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses are successfully replicated in the independent sample. Conclusions: This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risk. More experiments or larger samples are needed to validate their contribution to the pathogenic mechanism of HCC.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
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