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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Ried, Janina S.; Jeff, Janina M.; Chu, Audrey Y.; Bragg-Gresham, Jennifer L.; Van Dongen, Jenny; Huffman, Jennifer E.; Ahluwalia, Tarunveer S.; Cadby, Gemma; Eklund, Niina and Eriksson, Joel, et al. (2016) In Nature Communications 7.
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-analysed summary statistics. We identify six... (More)

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-analysed 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.

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Nature Communications
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7
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Nature Publishing Group
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  • scopus:85000900079
  • wos:000388319700001
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2041-1723
DOI
10.1038/ncomms13357
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English
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07f751f5-3bc7-4e81-a03e-c72b40a4600c
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2017-01-02 10:24:10
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@article{07f751f5-3bc7-4e81-a03e-c72b40a4600c,
  abstract     = {<p>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 &gt;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-analysed 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.</p>},
  articleno    = {13357},
  author       = {Ried, Janina S. and Jeff, Janina M. and Chu, Audrey Y. and Bragg-Gresham, Jennifer L. and Van Dongen, Jenny and Huffman, Jennifer E. and Ahluwalia, Tarunveer S. and Cadby, Gemma and Eklund, Niina and Eriksson, Joel and Esko, Toñu and Feitosa, Mary F. and Goel, Anuj and Gorski, Mathias and Hayward, Caroline and Heard-Costa, Nancy L. and Jackson, Anne U. and Jokinen, Eero and Kanoni, Stavroula and Kristiansson, Kati and Kutalik, Zoltán and Lahti, Jari and Luan, Jian'an and Mägi, Reedik and Mahajan, Anubha and Mangino, Massimo and Medina-Gomez, Carolina and Monda, Keri L. and Nolte, Ilja M. and Pérusse, Louis and Prokopenko, Inga and Qi, Lu and Rose, Lynda M. and Salvi, Erika and Smith, Megan T. and Snieder, Harold and Standáková, Alena and Ju Sung, Yun and Tachmazidou, Ioanna and Teumer, Alexander and Thorleifsson, Gudmar and Van Der Harst, Pim and Walker, Ryan W. and Wang, Sophie R. and Wild, Sarah H. and Willems, Sara M. and Wong, Andrew and Zhang, Weihua and Albrecht, Eva and Couto Alves, Alexessander and Bakker, Stephan J L and Barlassina, Cristina and Bartz, Traci M. and Beilby, John and Bellis, Claire and Bergman, Richard N. and Bergmann, Sven and Blangero, John and Blüher, Matthias and Boerwinkle, Eric and Bonnycastle, Lori L. and Bornstein, Stefan R. and Bruinenberg, Marcel and Campbell, Harry and Chen, Yii Der Ida and Chiang, Charleston W K and Chines, Peter S. and Collins, Francis S. and Cucca, Fracensco and Cupples, L. 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  issn         = {2041-1723},
  language     = {eng},
  month        = {11},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape},
  url          = {http://dx.doi.org/10.1038/ncomms13357},
  volume       = {7},
  year         = {2016},
}