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

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Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Van Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J et al (show 90 more authors) , Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU ORCID: 0000-0002-9672-2547, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, J, Mägi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM ORCID: 0000-0001-5047-4077, Pérusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, MT, Snieder, H, Standáková, A, Ju Sung, Y, Tachmazidou, I, Teumer, A, Thorleifsson, G, Van Der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, SM, Wong, A ORCID: 0000-0003-2079-4779, Zhang, W, Albrecht, E, Couto Alves, A, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Blüher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'avila, F, De Geus, EJC, Dedoussis, G, Dimitriou, M, Döring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Gräßler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliövaara, M, Hillege, H, Hofman, A and Holmen, O (2016) A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape Nature Communications, 7 (1). 13357-. ISSN 2041-1723, 2041-1723

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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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Anthropometry, Body Size, Genotype, Principal Component Analysis, Models, Genetic, Genome-Wide Association Study
Depositing User:	Symplectic Admin
Date Deposited:	17 Jan 2017 08:22
Last Modified:	01 Mar 2026 05:34
DOI:	10.1038/ncomms13357
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3005273
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