title: A combined reference panel from the 1000 Genomes and UK10K projects improved rare variant imputation in European and Chinese samples.
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.
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.|Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chou
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University, and the Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Hou-Feng
authors.initials: HF
authors.lastname: Zheng
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Chia-Ho
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Department of Pulmonary, Critical Care Medicine, Peking University People's Hospital, Beijing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University, and the Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pulmonary, Critical Care Medicine, Peking University People's Hospital, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.|Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Karasik
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.|Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Kiel
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.|Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
mesh_terms: D002681:China; D005060:Europe; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods* / Q000592:standards*; D006801:Humans; D012015:Reference Standards