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

Janina S. Ried; Janina M. Jeff; Audrey Y. Chu; Jennifer L. Bragg-Gresham; Jenny van Dongen; Jennifer E. Huffman; Tarunveer S. Ahluwalia; Gemma Cadby; Niina Eklund; Joel Eriksson; Tonu Esko; Mary F. Feitosa; Anuj Goel; Mathias Gorski; Caroline Hayward; Nancy L. Heard-Costa; Anne U. Jackson; Eero Jokinen; Stavroula Kanoni; Kati Kristiansson; Zoltan Kutalik; Jari Lahti; Jian'an Luan; Reedik Maegi; Anubha Mahajan; Massimo Mangino; Carolina Medina-Gomez; Keri L. Monda; Ilja M. Nolte; Louis Perusse; Inga Prokopenko; Lu Qi; Lynda M. Rose; Erika Salvi; Megan T. Smith; Harold Snieder; Alena Stancakova; Yun Ju Sung; Ioanna Tachmazidou; Alexander Teumer; Gudmar Thorleifsson; Pim van der Harst; Ryan W. Walker; Sophie R. Wang; Sarah H. Wild; Sara M. Willems; Andrew Wong; Weihua Zhang; Eva Albrecht; Aaron Isaacs; Author collaboration; Ruth J.F. Roos

doi:10.1038/ncomms13357

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

Janina S. Ried, Janina M. Jeff, Audrey Y. Chu, Jennifer L. Bragg-Gresham, Jenny van Dongen, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, Tonu Esko, Mary F. Feitosa, Anuj Goel, Mathias Gorski, Caroline Hayward, Nancy L. Heard-Costa, Anne U. Jackson, Eero Jokinen, Stavroula Kanoni, Kati KristianssonZoltan Kutalik, Jari Lahti, Jian'an Luan, Reedik Maegi, Anubha Mahajan, Massimo Mangino, Carolina Medina-Gomez, Keri L. Monda, Ilja M. Nolte, Louis Perusse, Inga Prokopenko, Lu Qi, Lynda M. Rose, Erika Salvi, Megan T. Smith, Harold Snieder, Alena Stancakova, Yun Ju Sung, Ioanna Tachmazidou, Alexander Teumer, Gudmar Thorleifsson, Pim van der Harst, Ryan W. Walker, Sophie R. Wang, Sarah H. Wild, Sara M. Willems, Andrew Wong, Weihua Zhang, Eva Albrecht, Aaron Isaacs, Author collaboration, Ruth J.F. Roos^*

^*Corresponding author for this work

Biochemie

Research output: Contribution to journal › Article › Academic › peer-review

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 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.

Original language	English
Number of pages	11
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13357
Publication status	Published - 23 Nov 2016

Keywords

Genome-wide association
Diet-induced obesity
Early-onset
Mass index
Hip ratio
Resource
Common
Mice
Snp

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10.1038/ncomms13357Licence: CC BY

Cite this

Ried, J. S., Jeff, J. M., Chu, A. Y., Bragg-Gresham, J. L., van Dongen, J., Huffman, J. E., Ahluwalia, T. S., Cadby, G., Eklund, N., Eriksson, J., Esko, T., Feitosa, M. F., Goel, A., Gorski, M., Hayward, C., Heard-Costa, N. L., Jackson, A. U., Jokinen, E., Kanoni, S., ... Roos, R. J. F. (2016). A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. Nature Communications, 7. https://doi.org/10.1038/ncomms13357

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

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 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.",

keywords = "Genome-wide association, Diet-induced obesity, Early-onset, Mass index, Hip ratio, Resource, Common, Mice, Snp",

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 Gemma Cadby and Niina Eklund and Joel Eriksson and Tonu Esko and Feitosa, {Mary F.} and Anuj Goel and Mathias Gorski and Caroline Hayward and Heard-Costa, {Nancy L.} and Jackson, {Anne U.} and Eero Jokinen and Stavroula Kanoni and Kati Kristiansson and Zoltan Kutalik and Jari Lahti and Jian'an Luan and Reedik Maegi and Anubha Mahajan and Massimo Mangino and Carolina Medina-Gomez and Monda, {Keri L.} and Nolte, {Ilja M.} and Louis Perusse and Inga Prokopenko and Lu Qi and Rose, {Lynda M.} and Erika Salvi and Smith, {Megan T.} and Harold Snieder and Alena Stancakova and Sung, {Yun Ju} and Ioanna Tachmazidou and Alexander Teumer and Gudmar Thorleifsson and {van der Harst}, Pim and Walker, {Ryan W.} and Wang, {Sophie R.} and Wild, {Sarah H.} and Willems, {Sara M.} and Andrew Wong and Weihua Zhang and Eva Albrecht and Aaron Isaacs and {Author collaboration} and Roos, {Ruth J.F.}",

year = "2016",

month = nov,

day = "23",

doi = "10.1038/ncomms13357",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, van Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, J, Maegi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM, Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, MT, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, SM, Wong, A, Zhang, W, Albrecht, E, Isaacs, A, Author collaboration & Roos, RJF 2016, 'A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape', Nature Communications, vol. 7. https://doi.org/10.1038/ncomms13357

TY - JOUR

T1 - A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

AU - Ried, Janina S.

AU - Jeff, Janina M.

AU - Chu, Audrey Y.

AU - Bragg-Gresham, Jennifer L.

AU - van Dongen, Jenny

AU - Huffman, Jennifer E.

AU - Ahluwalia, Tarunveer S.

AU - Cadby, Gemma

AU - Eklund, Niina

AU - Eriksson, Joel

AU - Esko, Tonu

AU - Feitosa, Mary F.

AU - Goel, Anuj

AU - Gorski, Mathias

AU - Hayward, Caroline

AU - Heard-Costa, Nancy L.

AU - Jackson, Anne U.

AU - Jokinen, Eero

AU - Kanoni, Stavroula

AU - Kristiansson, Kati

AU - Kutalik, Zoltan

AU - Lahti, Jari

AU - Luan, Jian'an

AU - Maegi, Reedik

AU - Mahajan, Anubha

AU - Mangino, Massimo

AU - Medina-Gomez, Carolina

AU - Monda, Keri L.

AU - Nolte, Ilja M.

AU - Perusse, Louis

AU - Prokopenko, Inga

AU - Qi, Lu

AU - Rose, Lynda M.

AU - Salvi, Erika

AU - Smith, Megan T.

AU - Snieder, Harold

AU - Stancakova, Alena

AU - Sung, Yun Ju

AU - Tachmazidou, Ioanna

AU - Teumer, Alexander

AU - Thorleifsson, Gudmar

AU - van der Harst, Pim

AU - Walker, Ryan W.

AU - Wang, Sophie R.

AU - Wild, Sarah H.

AU - Willems, Sara M.

AU - Wong, Andrew

AU - Zhang, Weihua

AU - Albrecht, Eva

AU - Isaacs, Aaron

AU - Author collaboration

AU - Roos, Ruth J.F.

PY - 2016/11/23

Y1 - 2016/11/23

N2 - 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.

AB - 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.

KW - Genome-wide association

KW - Diet-induced obesity

KW - Early-onset

KW - Mass index

KW - Hip ratio

KW - Resource

KW - Common

KW - Mice

KW - Snp

U2 - 10.1038/ncomms13357

DO - 10.1038/ncomms13357

M3 - Article

C2 - 27876822

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

ER -