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.

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape / J.S. Ried, J. Jeff M, A.Y. Chu, J.L. Bragg Gresham, J. van Dongen, J.E. Huffman, T.S. Ahluwalia, G. Cadby, N. Eklund, J. Eriksson, T. Esko, M.F. Feitosa, A. Goel, M. Gorski, C. Hayward, N.L. Heard Costa, A.U. Jackson, E. Jokinen, S. Kanoni, K. Kristiansson, Z. Kutalik, J. Lahti, J. Luan, R. Mägi, A. Mahajan, M. Mangino, C. Medina Gomez, K.L. Monda, I.M. Nolte, L. Pérusse, I. Prokopenko, L. Qi, L.M. Rose, E. Salvi, M.T. Smith, H. Snieder, A. Stančáková, Y. Ju Sung, I. Tachmazidou, A. Teumer, G. Thorleifsson, P. van der Harst, R.W. Walker, S.R. Wang, S.H. Wild, S.M. Willems, A. Wong, W. Zhang, E. Albrecht, A. Couto Alves, S.J.L. Bakker, C. Barlassina, T.M. Bartz, J. Beilby, C. Bellis, R.N. Bergman, S. Bergmann, J. Blangero, M. Blüher, E. Boerwinkle, L.L. Bonnycastle, S.R. Bornstein, M. Bruinenberg, H. Campbell, Y.I. Chen, C.W.K. Chiang, P.S. Chines, F.S. Collins, F. Cucca, L.A. Cupples, F. D'Avila, E.J.C. de Geus, G. Dedoussis, M. Dimitriou, A. Döring, J.G. Eriksson, A. Farmaki, M. Farrall, T. Ferreira, K. Fischer, N.G. Forouhi, N. Friedrich, A.P. Gjesing, N. Glorioso, M. Graff, H. Grallert, N. Grarup, J. Gräßler, J. Grewal, A. Hamsten, M.N. Harder, C.A. Hartman, M. Hassinen, N. Hastie, A.T. Hattersley, A.S. Havulinna, M. Heliövaara, H. Hillege, A. Hofman, O. Holmen, G. Homuth, J. Hottenga, J. Hui, L.L. Husemoen, P.G. Hysi, A. Isaacs, T. Ittermann, S. Jalilzadeh, A.L. James, T. Jørgensen, P. Jousilahti, A. Jula, J. Marie Justesen, A.E. Justice, M. Kähönen, M. Karaleftheri, K. Tee Khaw, S.M. Keinanen Kiukaanniemi, L. Kinnunen, P.B. Knekt, H.A. Koistinen, I. Kolcic, I.K. Kooner, S. Koskinen, P. Kovacs, T. Kyriakou, T. Laitinen, C. Langenberg, A.M. Lewin, P. Lichtner, C.M. Lindgren, J. Lindström, A. Linneberg, R. Lorbeer, M. Lorentzon, R. Luben, V. Lyssenko, S. Männistö, P. Manunta, I.M. Leach, W.L. Mcardle, B. Mcknight, K.L. Mohlke, E. Mihailov, L. Milani, R. Mills, M.E. Montasser, A.P. Morris, G. Müller, A.W. Musk, N. Narisu, K.K. Ong, B.A. Oostra, C. Osmond, A. Palotie, J.S. Pankow, L. Paternoster, B.W. Penninx, I. Pichler, M.G. Pilia, O. Polašek, P.P. Pramstaller, O.T. Raitakari, T. Rankinen, D.C. Rao, N.W. Rayner, R. Ribel Madsen, T.K. Rice, M. Richards, P.M. Ridker, F. Rivadeneira, K.A. Ryan, S. Sanna, M.A. Sarzynski, S. Scholtens, R.A. Scott, S. Sebert, L. Southam, T.H. Sparsø, V. Steinthorsdottir, K. Stirrups, R.P. Stolk, K. Strauch, H.M. Stringham, M.A. Swertz, A.J. Swift, A. Tönjes, E. Tsafantakis, P.J. van der Most, J.V. Van Vliet Ostaptchouk, L. Vandenput, E. Vartiainen, C. Venturini, N. Verweij, J.S. Viikari, V. Vitart, M. Vohl, J.M. Vonk, G. Waeber, E. Widén, G. Willemsen, T. Wilsgaard, T.W. Winkler, A.F. Wright, L.M. Yerges Armstrong, J. Hua Zhao, M. Carola Zillikens, D.I. Boomsma, C. Bouchard, J.C. Chambers, D.I. Chasman, D. Cusi, R.T. Gansevoort, C. Gieger, T. Hansen, A.A. Hicks, F. Hu, K. Hveem, M. Jarvelin, E. Kajantie, J.S. Kooner, D. Kuh, J. Kuusisto, M. Laakso, T.A. Lakka, T. Lehtimäki, A. Metspalu, I. Njølstad, C. Ohlsson, A.J. Oldehinkel, L.J. Palmer, O. Pedersen, M. Perola, A. Peters, B.M. Psaty, H. Puolijoki, R. Rauramaa, I. Rudan, V. Salomaa, P.E.H. Schwarz, A.R. Shudiner, J.H. Smit, T.I.A. Sørensen, T.D. Spector, K. Stefansson, M. Stumvoll, A. Tremblay, J. Tuomilehto, A.G. Uitterlinden, M. Uusitupa, U. Völker, P. Vollenweider, N.J. Wareham, H. Watkins, J.F. Wilson, E. Zeggini, G.R. Abecasis, M. Boehnke, I.B. Borecki, P. Deloukas, C.M. van Duijn, C. Fox, L.C. Groop, I.M. Heid, D.J. Hunter, R.C. Kaplan, M.I. Mccarthy, K.E. North, J.R. O'Connell, D. Schlessinger, U. Thorsteinsdottir, D.P. Strachan, T. Frayling, J.N. Hirschhorn, M. Müller Nurasyid, R.J.F. Loos. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 7(2016 Nov 23). [10.1038/ncomms13357]

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

E. Salvi;C. Barlassina;F. D'Avila;D. Cusi;
2016-11-23

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.
Settore MED/03 - Genetica Medica
Settore BIO/18 - Genetica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/462905
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