Impact of pre- and post-variant filtration strategies on imputation

Abstract Quality control (QC) 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 n...

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Autores principales:	Céline Charon, Rodrigue Allodji, Vincent Meyer, Jean-François Deleuze
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2730f7d8a71343b285772a9c544f1ed0
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spelling	oai:doaj.org-article:2730f7d8a71343b285772a9c544f1ed02021-12-02T17:04:59ZImpact of pre- and post-variant filtration strategies on imputation10.1038/s41598-021-85333-z2045-2322https://doaj.org/article/2730f7d8a71343b285772a9c544f1ed02021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85333-zhttps://doaj.org/toc/2045-2322Abstract Quality control (QC) 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 1031 genotyped individuals from diverse ethnicities and compared the imputed variants to 1089 NCBI recorded individuals for additional validation. Without QC-based variant pre-filtration, 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). Thus, to maintain confidence and enough SNVs, we propose here a two-step filtering procedure which allows less stringent filtering prior to imputation and post-imputation in order to increase the number of very rare and rare variants compared to conservative filtration methods.Céline CharonRodrigue AllodjiVincent MeyerJean-François DeleuzeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Céline Charon Rodrigue Allodji Vincent Meyer Jean-François Deleuze Impact of pre- and post-variant filtration strategies on imputation
description	Abstract Quality control (QC) 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 1031 genotyped individuals from diverse ethnicities and compared the imputed variants to 1089 NCBI recorded individuals for additional validation. Without QC-based variant pre-filtration, 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). Thus, to maintain confidence and enough SNVs, we propose here a two-step filtering procedure which allows less stringent filtering prior to imputation and post-imputation in order to increase the number of very rare and rare variants compared to conservative filtration methods.
format	article
author	Céline Charon Rodrigue Allodji Vincent Meyer Jean-François Deleuze
author_facet	Céline Charon Rodrigue Allodji Vincent Meyer Jean-François Deleuze
author_sort	Céline Charon
title	Impact of pre- and post-variant filtration strategies on imputation
title_short	Impact of pre- and post-variant filtration strategies on imputation
title_full	Impact of pre- and post-variant filtration strategies on imputation
title_fullStr	Impact of pre- and post-variant filtration strategies on imputation
title_full_unstemmed	Impact of pre- and post-variant filtration strategies on imputation
title_sort	impact of pre- and post-variant filtration strategies on imputation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2730f7d8a71343b285772a9c544f1ed0
work_keys_str_mv	AT celinecharon impactofpreandpostvariantfiltrationstrategiesonimputation AT rodrigueallodji impactofpreandpostvariantfiltrationstrategiesonimputation AT vincentmeyer impactofpreandpostvariantfiltrationstrategiesonimputation AT jeanfrancoisdeleuze impactofpreandpostvariantfiltrationstrategiesonimputation
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Impact of pre- and post-variant filtration strategies on imputation

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