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Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits. / Tachmazidou, Ioanna; Süveges, Dániel; Min, Josine L. et al.
In:
American Journal of Human Genetics, Vol. 100, No. 6, 01.06.2017, p. 865–884.
Research output: Contribution to journal › Article › peer-review
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Tachmazidou, I, Süveges, D, Min, JL, Ritchie, GRS, Steinberg, J, Walter, K, Iotchkova, V, Schwartzentruber, J, Huang, J
, Memari, Y, McCarthy, S, Crawford, AA, Bombieri, C, Cocca, M, Farmaki, A-E, Gaunt, TR, Jousilahti, P, Kooijman, MN
, Lehne, B, Malerba, G, Männistö, S, Matchan, A, Medina-Gomez, C
, Metrustry, SJ, Nag, A, Ntalla, I, Paternoster, L, Rayner, NW, Sala, C, Scott, WR, Shihab, HA, Southam, L, St Pourcain, B, Traglia, M, Trajanoska, K, Zaza, G, Zhang, W, Artigas, MS, Bansal, N, Benn, M, Chen, Z, Danecek, P, Lin, W-Y, Locke, A, Luan, J, Manning, AK, Mulas, A, Sidore, C, Tybjaerg-Hansen, A, Varbo, A, Zoledziewska, M, Finan, C, Hatzikotoulas, K, Hendricks, AE, Kemp, JP
, Moayyeri, A, Panoutsopoulou, K, Szpak, M, Wilson, SG, Boehnke, M, Cucca, F, Di Angelantonio, E, Langenberg, C, Lindgren, C, McCarthy, MI, Morris, AP, Nordestgaard, BG, Scott, RA, Tobin, MD, Wareham, NJ, Burton, P
, Chambers, JC, Smith, GD, Dedoussis, G, Felix, JF, Franco, OH, Gambaro, G, Gasparini, P
, Hammond, CJ, Hofman, A, Jaddoe, VWV, Kleber, M, Kooner, JS, Perola, M, Relton, C, Ring, SM, Rivadeneira, F, Salomaa, V
, Spector, TD, Stegle, O, Toniolo, D, Uitterlinden, AG, Barroso, I, Greenwood, CMT, Perry, JRB, Walker, BR, Butterworth, AS, Xue, Y, Durbin, R
, Small, KS, Soranzo, N, Timpson, NJ & Zeggini, E 2017, '
Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits',
American Journal of Human Genetics, vol. 100, no. 6, pp. 865–884.
https://doi.org/10.1016/j.ajhg.2017.04.014APA
Tachmazidou, I., Süveges, D., Min, J. L., Ritchie, G. R. S., Steinberg, J., Walter, K., Iotchkova, V., Schwartzentruber, J., Huang, J.
, Memari, Y., McCarthy, S., Crawford, A. A., Bombieri, C., Cocca, M., Farmaki, A-E., Gaunt, T. R., Jousilahti, P., Kooijman, M. N.
, Lehne, B., ... Zeggini, E. (2017).
Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.
American Journal of Human Genetics,
100(6), 865–884.
https://doi.org/10.1016/j.ajhg.2017.04.014Vancouver
Tachmazidou I, Süveges D, Min JL, Ritchie GRS, Steinberg J, Walter K et al.
Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.
American Journal of Human Genetics. 2017 Jun 1;100(6):865–884.
https://doi.org/10.1016/j.ajhg.2017.04.014Author
Tachmazidou, Ioanna ; Süveges, Dániel ; Min, Josine L. et al. / Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits. In: American Journal of Human Genetics. 2017 ; Vol. 100, No. 6. pp. 865–884.
@article{0f44dfcf42bc48ebb22e27eb19ffbec0,
title = "Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits",
abstract = "Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.",
keywords = "UK10K, genetic association study, next-generation whole-genome sequencing, imputation, UK Biobank, anthropometry, DXA traits",
author = "Ioanna Tachmazidou and D{\'a}niel S{\"u}veges and Min, {Josine L.} and Ritchie, {Graham R.S.} and Julia Steinberg and Klaudia Walter and Valentina Iotchkova and Jeremy Schwartzentruber and Jie Huang and Yasin Memari and Shane McCarthy and Crawford, {Andrew A.} and Cristina Bombieri and Massimiliano Cocca and Aliki-Eleni Farmaki and Gaunt, {Tom R.} and Pekka Jousilahti and Kooijman, {Marjolein N.} and Benjamin Lehne and Giovanni Malerba and Satu M{\"a}nnist{\"o} and Angela Matchan and Carolina Medina-Gomez and Metrustry, {Sarah J.} and Abhishek Nag and Ioanna Ntalla and Lavinia Paternoster and Rayner, {Nigel W.} and Cinzia Sala and Scott, {William R.} and Shihab, {Hashem A.} and Lorraine Southam and {St Pourcain}, Beate and Michela Traglia and Katerina Trajanoska and Gialuigi Zaza and Weihua Zhang and Artigas, {Mar{\'i}a S.} and Narinder Bansal and Marianne Benn and Zhongsheng Chen and Petr Danecek and Wei-Yu Lin and Adam Locke and Jian{\textquoteright}an Luan and Manning, {Alisa K.} and Antonella Mulas and Carlo Sidore and Anne Tybjaerg-Hansen and Anette Varbo and Magdalena Zoledziewska and Chris Finan and Konstantinos Hatzikotoulas and Hendricks, {Audrey E.} and Kemp, {John P.} and Alireza Moayyeri and Kalliope Panoutsopoulou and Michal Szpak and Wilson, {Scott G.} and Michael Boehnke and Francesco Cucca and {Di Angelantonio}, Emanuele and Claudia Langenberg and Cecilia Lindgren and McCarthy, {Mark I.} and Morris, {Andrew P.} and Nordestgaard, {B{\o}rge G.} and Scott, {Robert A.} and Tobin, {Martin D.} and Wareham, {Nicholas J.} and Paul Burton and Chambers, {John C.} and Smith, {George Davey} and George Dedoussis and Felix, {Janine F.} and Franco, {Oscar H.} and Giovanni Gambaro and Paolo Gasparini and Hammond, {Christopher J.} and Albert Hofman and Jaddoe, {Vincent W.V.} and Marcus Kleber and Kooner, {Jaspal S.} and Markus Perola and Caroline Relton and Ring, {Susan M.} and Fernando Rivadeneira and Veikko Salomaa and Spector, {Timothy D.} and Oliver Stegle and Daniela Toniolo and Uitterlinden, {Andr{\'e} G.} and In{\^e}s Barroso and Greenwood, {Celia M.T.} and Perry, {John R.B.} and Walker, {Brian R.} and Butterworth, {Adam S.} and Yali Xue and Richard Durbin and Small, {Kerrin S.} and Nicole Soranzo and Timpson, {Nicholas J.} and Eleftheria Zeggini",
year = "2017",
month = jun,
day = "1",
doi = "10.1016/j.ajhg.2017.04.014",
language = "English",
volume = "100",
pages = "865–884",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Elsevier",
number = "6",
}
RIS (suitable for import to EndNote) Download
TY - JOUR
T1 - Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits
AU - Tachmazidou, Ioanna
AU - Süveges, Dániel
AU - Min, Josine L.
AU - Ritchie, Graham R.S.
AU - Steinberg, Julia
AU - Walter, Klaudia
AU - Iotchkova, Valentina
AU - Schwartzentruber, Jeremy
AU - Huang, Jie
AU - Memari, Yasin
AU - McCarthy, Shane
AU - Crawford, Andrew A.
AU - Bombieri, Cristina
AU - Cocca, Massimiliano
AU - Farmaki, Aliki-Eleni
AU - Gaunt, Tom R.
AU - Jousilahti, Pekka
AU - Kooijman, Marjolein N.
AU - Lehne, Benjamin
AU - Malerba, Giovanni
AU - Männistö, Satu
AU - Matchan, Angela
AU - Medina-Gomez, Carolina
AU - Metrustry, Sarah J.
AU - Nag, Abhishek
AU - Ntalla, Ioanna
AU - Paternoster, Lavinia
AU - Rayner, Nigel W.
AU - Sala, Cinzia
AU - Scott, William R.
AU - Shihab, Hashem A.
AU - Southam, Lorraine
AU - St Pourcain, Beate
AU - Traglia, Michela
AU - Trajanoska, Katerina
AU - Zaza, Gialuigi
AU - Zhang, Weihua
AU - Artigas, María S.
AU - Bansal, Narinder
AU - Benn, Marianne
AU - Chen, Zhongsheng
AU - Danecek, Petr
AU - Lin, Wei-Yu
AU - Locke, Adam
AU - Luan, Jian’an
AU - Manning, Alisa K.
AU - Mulas, Antonella
AU - Sidore, Carlo
AU - Tybjaerg-Hansen, Anne
AU - Varbo, Anette
AU - Zoledziewska, Magdalena
AU - Finan, Chris
AU - Hatzikotoulas, Konstantinos
AU - Hendricks, Audrey E.
AU - Kemp, John P.
AU - Moayyeri, Alireza
AU - Panoutsopoulou, Kalliope
AU - Szpak, Michal
AU - Wilson, Scott G.
AU - Boehnke, Michael
AU - Cucca, Francesco
AU - Di Angelantonio, Emanuele
AU - Langenberg, Claudia
AU - Lindgren, Cecilia
AU - McCarthy, Mark I.
AU - Morris, Andrew P.
AU - Nordestgaard, Børge G.
AU - Scott, Robert A.
AU - Tobin, Martin D.
AU - Wareham, Nicholas J.
AU - Burton, Paul
AU - Chambers, John C.
AU - Smith, George Davey
AU - Dedoussis, George
AU - Felix, Janine F.
AU - Franco, Oscar H.
AU - Gambaro, Giovanni
AU - Gasparini, Paolo
AU - Hammond, Christopher J.
AU - Hofman, Albert
AU - Jaddoe, Vincent W.V.
AU - Kleber, Marcus
AU - Kooner, Jaspal S.
AU - Perola, Markus
AU - Relton, Caroline
AU - Ring, Susan M.
AU - Rivadeneira, Fernando
AU - Salomaa, Veikko
AU - Spector, Timothy D.
AU - Stegle, Oliver
AU - Toniolo, Daniela
AU - Uitterlinden, André G.
AU - Barroso, Inês
AU - Greenwood, Celia M.T.
AU - Perry, John R.B.
AU - Walker, Brian R.
AU - Butterworth, Adam S.
AU - Xue, Yali
AU - Durbin, Richard
AU - Small, Kerrin S.
AU - Soranzo, Nicole
AU - Timpson, Nicholas J.
AU - Zeggini, Eleftheria
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.
AB - Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.
KW - UK10K
KW - genetic association study
KW - next-generation whole-genome sequencing
KW - imputation
KW - UK Biobank
KW - anthropometry
KW - DXA traits
U2 - 10.1016/j.ajhg.2017.04.014
DO - 10.1016/j.ajhg.2017.04.014
M3 - Article
VL - 100
SP - 865
EP - 884
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -