A combined reference panel from the 1000 Genomes and UK10K projects improved rare variant imputation in European and Chinese samples.

Sci Rep
Authors
Abstract

Imputation using the 1000 Genomes haplotype reference panel has been widely adapted to estimate genotypes in genome wide association studies. To evaluate imputation quality with a relatively larger reference panel and a reference panel composed of different ethnic populations, we conducted imputations in the Framingham Heart Study and the North Chinese Study using a combined reference panel from the 1000 Genomes (N = 1,092) and UK10K (N = 3,781) projects. For rare variants with 0.01%  MAF ≤ 0.5%, imputation in the Framingham Heart Study with the combined reference panel increased well-imputed genotypes (with imputation quality score ≥0.4) from 62.9% to 76.1% when compared to imputation with the 1000 Genomes. For the North Chinese samples, imputation of rare variants with 0.01%  MAF ≤ 0.5% with the combined reference panel increased well-imputed genotypes by from 49.8% to 61.8%. The predominant European ancestry of the UK10K and the combined reference panels may explain why there was less of an increase in imputation success in the North Chinese samples. Our results underscore the importance and potential of larger reference panels to impute rare variants, while recognizing that increasing ethnic specific variants in reference panels may result in better imputation for genotypes in some ethnic groups.

Year of Publication
2016
Journal
Sci Rep
Volume
6
Pages
39313
Date Published
2016 Dec 22
ISSN
2045-2322
DOI
10.1038/srep39313
PubMed ID
28004816
PubMed Central ID
PMC5177868
Links
Grant list
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 AR041398 / AR / NIAMS NIH HHS / United States
R01 AR061162 / AR / NIAMS NIH HHS / United States
R01 AR061445 / AR / NIAMS NIH HHS / United States