%0 Journal Article %T Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits %A Abhishek Nag %A Adam Locke %A Adam S. Butterworth %A Albert Hofman %A Aliki-Eleni Farmaki %A Alireza Moayyeri %A Alisa K. Manning %A Andrew A. Crawford %A Andrew P. Morris %A Andr¨¦ G. Uitterlinden %A Anette Varbo %A Angela Matchan %A Anne Tybjaerg-Hansen %A Antonella Mulas %A Audrey E. Hendricks %A Beate St Pourcain %A Benjamin Lehne %A Brian R. Walker %A B£¿rge G. Nordestgaard %A Carlo Sidore %A Carolina Medina-Gomez %A Caroline Relton %A Cecilia Lindgren %A Celia M.T. Greenwood %A Chris Finan %A Christopher J. Hammond %A Cinzia Sala %A Claudia Langenberg %A Cristina Bombieri %A Daniela Toniolo %A D¨¢niel S¨¹veges %A Emanuele Di Angelantonio %A Fernando Rivadeneira %A Francesco Cucca %A George Davey Smith %A George Dedoussis %A Gialuigi Zaza %A Giovanni Gambaro %A Giovanni Malerba %A GoT2D Consortium %A Graham R.S. Ritchie %A Hashem A. Shihab %A In¨ºs Barroso %A Ioanna Ntalla %A Ioanna Tachmazidou %A Janine F. Felix %A Jaspal S. Kooner %A Jeremy Schwartzentruber %A Jian¡¯an Luan %A Jie Huang %A John C. Chambers %A John P. Kemp %A John R.B. Perry %A Josine L. Min %A Julia Steinberg %A Kalliope Panoutsopoulou %A Katerina Trajanoska %A Kerrin S. Small %A Klaudia Walter %A Konstantinos Hatzikotoulas %A Lavinia Paternoster %A Lorraine Southam %A Magdalena Zoledziewska %A Marcus Kleber %A Marianne Benn %A Marjolein N. Kooijman %A Mark I. McCarthy %A Markus Perola %A Martin D. Tobin %A Mar¨ªa S. Artigas %A Massimiliano Cocca %A Michael Boehnke %A Michal Szpak %A Michela Traglia %A Narinder Bansal %A Nicholas J. Timpson %A Nicholas J. Wareham %A Nicole Soranzo %A Nigel W. Rayner %A Oliver Stegle %A Oscar H. Franco %A Paolo Gasparini %A Paul Burton %A Pekka Jousilahti %A Petr Danecek %A Richard Durbin %A Robert A. Scott %A Sarah J. Metrustry %J Archive of "American Journal of Human Genetics". %D 2017 %R 10.1016/j.ajhg.2017.04.014 %X 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 %K UK10K %K genetic association study %K next-generation whole-genome sequencing %K imputation %K UK Biobank %K anthropometry %K DXA traits %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473732/