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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape in >170,000 individuals of the GIANT Consortium

Abstract:
Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analyzed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/ncomms13357

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Cardiovascular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Human Genetics Wt Centre
Role:
Author


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
7
Pages:
13357
Publication date:
2016-11-01
Acceptance date:
2016-09-21
DOI:
ISSN:
2041-1723


Pubs id:
pubs:652699
UUID:
uuid:ffb534c7-63bd-4eb7-a95f-086127a17ab1
Local pid:
pubs:652699
Source identifiers:
652699
Deposit date:
2016-10-17

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