Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies

Peter Joshi; James Prendergast; Ross M Fraser; Jennifer E Huffman; Veronique Vitart; Caroline Hayward; Ruth McQuillan; Dominik Glodzik; Ozren Polašek; Nicholas D Hastie; Igor Rudan; Harry Campbell; Alan F Wright; Chris S Haley; James F Wilson; Pau Navarro

doi:10.1371/journal.pone.0068604

Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies

Peter Joshi, James Prendergast, Ross M Fraser, Jennifer E Huffman, Veronique Vitart, Caroline Hayward, Ruth McQuillan, Dominik Glodzik, Ozren Polašek, Nicholas D Hastie, Igor Rudan, Harry Campbell, Alan F Wright, Chris S Haley, James F Wilson, Pau Navarro

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Abstract / Description of output

The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1-10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28-38%, for SNPs with a minor allele frequency in the range 1-3%.

Original language	English
Article number	e68604
Number of pages	6
Journal	PLoS ONE
Volume	8
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0068604
Publication status	Published - 16 Jul 2013

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10.1371/journal.pone.0068604

Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies
Copyright: © 2013 Joshi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0068604

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Joshi, P., Prendergast, J., Fraser, R. M., Huffman, J. E., Vitart, V., Hayward, C., McQuillan, R., Glodzik, D., Polašek, O., Hastie, N. D., Rudan, I., Campbell, H., Wright, A. F., Haley, C. S., Wilson, J. F., & Navarro, P. (2013). Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies. PLoS ONE, 8(7), Article e68604. https://doi.org/10.1371/journal.pone.0068604

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title = "Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies",

abstract = "The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1-10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28-38%, for SNPs with a minor allele frequency in the range 1-3%.",

author = "Peter Joshi and James Prendergast and Fraser, {Ross M} and Huffman, {Jennifer E} and Veronique Vitart and Caroline Hayward and Ruth McQuillan and Dominik Glodzik and Ozren Pola{\v s}ek and Hastie, {Nicholas D} and Igor Rudan and Harry Campbell and Wright, {Alan F} and Haley, {Chris S} and Wilson, {James F} and Pau Navarro",

note = " Funding: Wellcome Trust [095831] Medical Research Council [MC_PC_U127561128, MC_U127592696, MC_PC_U127592696] Chief Scientist Office [CZB/4/710] ",

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Joshi, P, Prendergast, J, Fraser, RM, Huffman, JE, Vitart, V , Hayward, C , McQuillan, R, Glodzik, D, Polašek, O, Hastie, ND, Rudan, I , Campbell, H, Wright, AF, Haley, CS , Wilson, JF & Navarro, P 2013, 'Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies', PLoS ONE, vol. 8, no. 7, e68604. https://doi.org/10.1371/journal.pone.0068604

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T1 - Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies

AU - Joshi, Peter

AU - Prendergast, James

AU - Fraser, Ross M

AU - Huffman, Jennifer E

AU - Vitart, Veronique

AU - Hayward, Caroline

AU - McQuillan, Ruth

AU - Glodzik, Dominik

AU - Polašek, Ozren

AU - Hastie, Nicholas D

AU - Rudan, Igor

AU - Campbell, Harry

AU - Wright, Alan F

AU - Haley, Chris S

AU - Wilson, James F

AU - Navarro, Pau

N1 - Funding: Wellcome Trust [095831] Medical Research Council [MC_PC_U127561128, MC_U127592696, MC_PC_U127592696] Chief Scientist Office [CZB/4/710]

PY - 2013/7/16

Y1 - 2013/7/16

N2 - The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1-10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28-38%, for SNPs with a minor allele frequency in the range 1-3%.

AB - The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1-10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28-38%, for SNPs with a minor allele frequency in the range 1-3%.

U2 - 10.1371/journal.pone.0068604

DO - 10.1371/journal.pone.0068604

M3 - Article

C2 - 23874685

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 7

M1 - e68604

ER -

Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies

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