Performance of genotype imputation for rare variants identified in exons and flanking regions of genes.

Détails

ID Serval
serval:BIB_7E0F9BFED1DF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Performance of genotype imputation for rare variants identified in exons and flanking regions of genes.
Périodique
Plos One
Auteur⸱e⸱s
Li L., Li Y., Browning S.R., Browning B.L., Slater A.J., Kong X., Aponte J.L., Mooser V.E., Chissoe S.L., Whittaker J.C., Nelson M.R., Ehm M.G.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2011
Volume
6
Numéro
9
Pages
e24945
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Genotype imputation has the potential to assess human genetic variation at a lower cost than assaying the variants using laboratory techniques. The performance of imputation for rare variants has not been comprehensively studied. We utilized 8865 human samples with high depth resequencing data for the exons and flanking regions of 202 genes and Genome-Wide Association Study (GWAS) data to characterize the performance of genotype imputation for rare variants. We evaluated reference sets ranging from 100 to 3713 subjects for imputing into samples typed for the Affymetrix (500K and 6.0) and Illumina 550K GWAS panels. The proportion of variants that could be well imputed (true r(2)>0.7) with a reference panel of 3713 individuals was: 31% (Illumina 550K) or 25% (Affymetrix 500K) with MAF (Minor Allele Frequency) less than or equal 0.001, 48% or 35% with 0.001<MAF< = 0.005, 54% or 38% with 0.005<MAF< = 0.01, 78% or 57% with 0.01<MAF< = 0.05, and 97% or 86% with MAF>0.05. The performance for common SNPs (MAF>0.05) within exons and flanking regions is comparable to imputation of more uniformly distributed SNPs. The performance for rare SNPs (0.01<MAF< = 0.05) was much more dependent on the GWAS panel and the number of reference samples. These results suggest routine use of genotype imputation for extending the assessment of common variants identified in humans via targeted exon resequencing into additional samples with GWAS data, but imputation of very rare variants (MAF< = 0.005) will require reference panels with thousands of subjects.
Mots-clé
Exons/genetics, Gene Frequency, Genes/genetics, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/03/2012 9:44
Dernière modification de la notice
20/08/2019 14:39
Données d'usage