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  4. Whole-genome sequencing coupled to imputation discovers genetic signals for anthropometric traits
 
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Whole-genome sequencing coupled to imputation discovers genetic signals for anthropometric traits
File(s)
1-s2.0-S0002929717301593-main.pdf (2.75 MB)
Published version
Author(s)
Tachmazidou, I
Suveges, D
Min, JL
Ritchie, GRS
Steinberg, J
more
Type
Journal Article
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.
Date Issued
2017-05-25
Date Acceptance
2017-04-21
Citation
American Journal of Human Genetics, 2017, 100 (6), pp.865-884
URI
http://hdl.handle.net/10044/1/49580
DOI
https://www.dx.doi.org/10.1016/j.ajhg.2017.04.014
ISSN
0002-9297
Publisher
University of Chicago Press
Start Page
865
End Page
884
Journal / Book Title
American Journal of Human Genetics
Volume
100
Issue
6
Copyright Statement
© 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000402700600004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
ADULT HUMAN HEIGHT
WIDE ASSOCIATION
TARGETED DISRUPTION
RARE VARIANTS
KNOCKOUT MICE
HOMEOBOX GENE
LOW-FREQUENCY
OBESITY
DISEASE
LOCI
Publication Status
Published
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