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Research Article
Impact of Pre and Post Variant Filtration Strategies on Imputation
Celine Charon
CEA Paris Saclay
Corresponding Author
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Quality control methods for genome-wide association studies and fine mapping are commonly used for imputation, however, they result in loss of many single nucleotide polymorphisms (SNPs). To investigate the consequences of filtration on imputation, we studied the direct effects on the number of markers, their allele frequencies, imputation quality scores and post-filtration events. We pre-phrased 1,031 genotyped individuals from diverse ethnicities and compared the imputed variants to 1,089 NCBI recorded individuals for additional validation.
Without variant pre-filtration based on quality control (QC), we observed no impairment in the imputation of SNPs that failed QC whereas with pre-filtration there was an overall loss of information. Significant differences between frequencies with and without pre-filtration were found only in the range of very rare (5E-04-1E-03) and rare variants (1E-03-5E-03) (p < 1E-04). Increasing the post-filtration imputation quality score from 0.3 to 0.8 reduced the number of single nucleotide variants (SNVs) <0.001 2.5 fold with or without QC pre-filtration and halved the number of very rare variants (5E-04). As a result, to maintain confidence and enough SNVs, we propose here a 2-step post-filtration approach to increase the number of very rare and rare variants compared to conservative post-filtration methods.
Keywords
Imputation, SNVs, filtrations, quality control, database, diverse populations, 1000 genome
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Due to technical limitations, table 1,2 is only available as a download in the Supplemental Files section.
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- SciRepSupplementaryMaterials14122020.pdf
Supplementary document
- Table1.jpg
- Table2.jpg
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On 28 Dec, 2020
Reviewer #3 agreed
On 28 Dec, 2020
Reviewer #1 agreed
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On 28 Dec, 2020
Reviewer #2 agreed
On 28 Dec, 2020
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This preprint is under consideration at Scientific Reports. A preprint is 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
Impact of Pre and Post Variant Filtration Strategies on Imputation
Celine Charon
CEA Paris Saclay
Corresponding Author
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: Under Revision
Version 1
Posted 21 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 11 Jan, 2021
Review #3 received
Received 10 Jan, 2021
Review #1 received
Received 10 Jan, 2021
Review #2 received
Received 10 Jan, 2021
Reviewer #5 agreed
On 28 Dec, 2020
Reviewer #3 agreed
On 28 Dec, 2020
Reviewer #1 agreed
On 28 Dec, 2020
Reviewer #4 agreed
On 28 Dec, 2020
Reviewer #2 agreed
On 28 Dec, 2020
Reviewers invited
Invitations sent on 24 Dec, 2020
Editor assigned
On 18 Dec, 2020
Editor invited
On 18 Dec, 2020
Submission checks complete
On 18 Dec, 2020
First submitted
On 14 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Quality control methods for genome-wide association studies and fine mapping are commonly used for imputation, however, they result in loss of many single nucleotide polymorphisms (SNPs). To investigate the consequences of filtration on imputation, we studied the direct effects on the number of markers, their allele frequencies, imputation quality scores and post-filtration events. We pre-phrased 1,031 genotyped individuals from diverse ethnicities and compared the imputed variants to 1,089 NCBI recorded individuals for additional validation.
Without variant pre-filtration based on quality control (QC), we observed no impairment in the imputation of SNPs that failed QC whereas with pre-filtration there was an overall loss of information. Significant differences between frequencies with and without pre-filtration were found only in the range of very rare (5E-04-1E-03) and rare variants (1E-03-5E-03) (p < 1E-04). Increasing the post-filtration imputation quality score from 0.3 to 0.8 reduced the number of single nucleotide variants (SNVs) <0.001 2.5 fold with or without QC pre-filtration and halved the number of very rare variants (5E-04). As a result, to maintain confidence and enough SNVs, we propose here a 2-step post-filtration approach to increase the number of very rare and rare variants compared to conservative post-filtration methods.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Due to technical limitations, table 1,2 is only available as a download in the Supplemental Files section.