Evaluation of the imputation performance of the program IMPUTE in an admixed sample from Mexico City using several model designs

We explored the imputation performance of the program IMPUTE in an admixed sample from Mexico City. The following issues were evaluated: (a) the impact of different reference panels (HapMap vs. 1000 Genomes) on imputation; (b) potential differences in imputation performance between single-step vs. t...

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Published in:BMC medical genomics 2012-05, Vol.5 (1), p.12-12, Article 12
Main Authors: Krithika, S, Valladares-Salgado, Adán, Peralta, Jesus, Escobedo-de La Peña, Jorge, Kumate-Rodríguez, Jesus, Cruz, Miguel, Parra, Esteban J
Format: Article
Language:English
Subjects:
Chromosomes
Comparative analysis
Gene Frequency - genetics
Genetic aspects
Genetic Markers - genetics
Genome, Human - genetics
Genomics
Genotype
Genotyping Techniques
HapMap Project
Humans
Mexico
Models, Statistical
Native Americans
Oligonucleotide Array Sequence Analysis
Physiological aspects
Reference Standards
Software
Type 2 diabetes
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cited_by cdi_FETCH-LOGICAL-b676t-c80f1774693cd9dbceabd5f278975f71dfecc3283a2cb579531e4f603004c9783
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Parra, Esteban J
description We explored the imputation performance of the program IMPUTE in an admixed sample from Mexico City. The following issues were evaluated: (a) the impact of different reference panels (HapMap vs. 1000 Genomes) on imputation; (b) potential differences in imputation performance between single-step vs. two-step (phasing and imputation) approaches; (c) the effect of different INFO score thresholds on imputation performance and (d) imputation performance in common vs. rare markers. The sample from Mexico City comprised 1,310 individuals genotyped with the Affymetrix 5.0 array. We randomly masked 5% of the markers directly genotyped on chromosome 12 (n=1,046) and compared the imputed genotypes with the microarray genotype calls. Imputation was carried out with the program IMPUTE. The concordance rates between the imputed and observed genotypes were used as a measure of imputation accuracy and the proportion of non-missing genotypes as a measure of imputation efficacy. The single-step imputation approach produced slightly higher concordance rates than the two-step strategy (99.1% vs. 98.4% when using the HapMap phase II combined panel), but at the expense of a lower proportion of non-missing genotypes (85.5% vs. 90.1%). The 1,000 Genomes reference sample produced similar concordance rates to the HapMap phase II panel (98.4% for both datasets, using the two-step strategy). However, the 1000 Genomes reference sample increased substantially the proportion of non-missing genotypes (94.7% vs. 90.1%). Rare variants (
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The following issues were evaluated: (a) the impact of different reference panels (HapMap vs. 1000 Genomes) on imputation; (b) potential differences in imputation performance between single-step vs. two-step (phasing and imputation) approaches; (c) the effect of different INFO score thresholds on imputation performance and (d) imputation performance in common vs. rare markers. The sample from Mexico City comprised 1,310 individuals genotyped with the Affymetrix 5.0 array. We randomly masked 5% of the markers directly genotyped on chromosome 12 (n=1,046) and compared the imputed genotypes with the microarray genotype calls. Imputation was carried out with the program IMPUTE. The concordance rates between the imputed and observed genotypes were used as a measure of imputation accuracy and the proportion of non-missing genotypes as a measure of imputation efficacy. The single-step imputation approach produced slightly higher concordance rates than the two-step strategy (99.1% vs. 98.4% when using the HapMap phase II combined panel), but at the expense of a lower proportion of non-missing genotypes (85.5% vs. 90.1%). The 1,000 Genomes reference sample produced similar concordance rates to the HapMap phase II panel (98.4% for both datasets, using the two-step strategy). However, the 1000 Genomes reference sample increased substantially the proportion of non-missing genotypes (94.7% vs. 90.1%). Rare variants (&lt;1%) had lower imputation accuracy and efficacy than common markers. The program IMPUTE had an excellent imputation performance for common alleles in an admixed sample from Mexico City, which has primarily Native American (62%) and European (33%) contributions. Genotype concordances were higher than 98.4% using all the imputation strategies, in spite of the fact that no Native American samples are present in the HapMap and 1000 Genomes reference panels. The best balance of imputation accuracy and efficiency was obtained with the 1,000 Genomes panel. 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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright ©2012 Krithika et al.; licensee BioMed Central Ltd. 2012 Krithika et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b676t-c80f1774693cd9dbceabd5f278975f71dfecc3283a2cb579531e4f603004c9783</citedby><cites>FETCH-LOGICAL-b676t-c80f1774693cd9dbceabd5f278975f71dfecc3283a2cb579531e4f603004c9783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436779/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1038365124?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22549150$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krithika, S</creatorcontrib><creatorcontrib>Valladares-Salgado, Adán</creatorcontrib><creatorcontrib>Peralta, Jesus</creatorcontrib><creatorcontrib>Escobedo-de La Peña, Jorge</creatorcontrib><creatorcontrib>Kumate-Rodríguez, Jesus</creatorcontrib><creatorcontrib>Cruz, Miguel</creatorcontrib><creatorcontrib>Parra, Esteban J</creatorcontrib><title>Evaluation of the imputation performance of the program IMPUTE in an admixed sample from Mexico City using several model designs</title><title>BMC medical genomics</title><addtitle>BMC Med Genomics</addtitle><description>We explored the imputation performance of the program IMPUTE in an admixed sample from Mexico City. 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The following issues were evaluated: (a) the impact of different reference panels (HapMap vs. 1000 Genomes) on imputation; (b) potential differences in imputation performance between single-step vs. two-step (phasing and imputation) approaches; (c) the effect of different INFO score thresholds on imputation performance and (d) imputation performance in common vs. rare markers. The sample from Mexico City comprised 1,310 individuals genotyped with the Affymetrix 5.0 array. We randomly masked 5% of the markers directly genotyped on chromosome 12 (n=1,046) and compared the imputed genotypes with the microarray genotype calls. Imputation was carried out with the program IMPUTE. The concordance rates between the imputed and observed genotypes were used as a measure of imputation accuracy and the proportion of non-missing genotypes as a measure of imputation efficacy. The single-step imputation approach produced slightly higher concordance rates than the two-step strategy (99.1% vs. 98.4% when using the HapMap phase II combined panel), but at the expense of a lower proportion of non-missing genotypes (85.5% vs. 90.1%). The 1,000 Genomes reference sample produced similar concordance rates to the HapMap phase II panel (98.4% for both datasets, using the two-step strategy). However, the 1000 Genomes reference sample increased substantially the proportion of non-missing genotypes (94.7% vs. 90.1%). Rare variants (&lt;1%) had lower imputation accuracy and efficacy than common markers. The program IMPUTE had an excellent imputation performance for common alleles in an admixed sample from Mexico City, which has primarily Native American (62%) and European (33%) contributions. Genotype concordances were higher than 98.4% using all the imputation strategies, in spite of the fact that no Native American samples are present in the HapMap and 1000 Genomes reference panels. The best balance of imputation accuracy and efficiency was obtained with the 1,000 Genomes panel. Rare variants were not captured effectively by any of the available panels, emphasizing the need to be cautious in the interpretation of association results for imputed rare variants.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>22549150</pmid><doi>10.1186/1755-8794-5-12</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Chromosomes
Comparative analysis
Gene Frequency - genetics
Genetic aspects
Genetic Markers - genetics
Genome, Human - genetics
Genomics
Genotype
Genotyping Techniques
HapMap Project
Humans
Mexico
Models, Statistical
Native Americans
Oligonucleotide Array Sequence Analysis
Physiological aspects
Reference Standards
Software
Type 2 diabetes
title Evaluation of the imputation performance of the program IMPUTE in an admixed sample from Mexico City using several model designs
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