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

Ried, JS; Jeff M, J; Chu, AY; Bragg-Gresham, JL; van Dongen, J; Huffman, JE; Ahluwalia, TS; Cadby, G; Eklund, N; Eriksson, J; Esko, T; Stolk, RP; Strauch, K; Stringham, HM; Swertz, MA; Swift, AJ; Tönjes, A; Tsafantakis, E; van der Most, PJ; Van Vliet-Ostaptchouk, JV; Kristiansson, K; Homuth, G; Vandenput, L; Vartiainen, E; Venturini, C; Verweij, N; Viikari, JS; Vitart, V; Vohl, M-C; Vonk, JM; Waeber, G; Widén, E; Hottenga, J-J; Kutalik, Z; Willemsen, G; Wilsgaard, T; Winkler, TW; Wright, AF; Yerges-Armstrong, LM; Hua Zhao, J; Carola Zillikens, M; Boomsma, DI; Bouchard, C; Hui, J; Chambers, JC; Lahti, J; Chasman, DI; Cusi, D; Gansevoort, RT; Gieger, C; Hansen, T; Hicks, AA; Hu, F; Hveem, K; Husemoen, LL; Jarvelin, M-R; Kajantie, E; Luan, J; Kooner, JS; Kuh, D; Kuusisto, J; Laakso, M; Lakka, TA; Lehtimäki, T; Metspalu, A; Hysi, PG; Njølstad, I; Ohlsson, C; Oldehinkel, AJ; Mägi, R; Palmer, LJ; Pedersen, O; Perola, M; Peters, A; Psaty, BM; Puolijoki, H; Isaacs, A; Rauramaa, R; Rudan, I; Salomaa, V; Schwarz, PEH; Mahajan, A; Shudiner, AR; Smit, JH; Sørensen, TIA; Spector, TD; Stefansson, K; Ittermann, T; Stumvoll, M; Tremblay, A; Tuomilehto, J; Uitterlinden, AG; Uusitupa, M; Mangino, M; Völker, U; Vollenweider, P; Wareham, NJ; Watkins, H; Jalilzadeh, S; Wilson, JF; Zeggini, E; Abecasis, GR; Boehnke, M; Borecki, IB; Deloukas, P; Medina-Gomez, C; van Duijn, CM; Fox, C; Groop, LC; James, AL; Heid, IM; Hunter, DJ; Kaplan, RC; McCarthy, MI; North, KE; O'Connell, JR; Schlessinger, D; Monda, KL; Thorsteinsdottir, U; Strachan, DP; Jørgensen, T; Frayling, T; Hirschhorn, JN; Müller-Nurasyid, M; Loos, RJF; Nolte, IM; Pérusse, L; Prokopenko, I; Qi, L; Rose, LM; Salvi, E; Feitosa, MF; Smith, MT; Snieder, H; Stančáková, A; Ju Sung, Y; Tachmazidou, I; Teumer, A; Thorleifsson, G; van der Harst, P; Walker, RW; Wang, SR; Jousilahti, P; Wild, SH; Willems, SM; Wong, A; Zhang, W; Albrecht, E; Couto Alves, A; Bakker, SJL; Barlassina, C; Bartz, TM; Beilby, J; Jula, A; Bellis, C; Bergman, RN; Bergmann, S; Blangero, J; Blüher, M; Boerwinkle, E; Bonnycastle, LL; Bornstein, SR; Bruinenberg, M; Campbell, H; Marie Justesen, J; Chen, Y-DI; Chiang, CWK; Chines, PS; Collins, FS; Cucca, F; Cupples, LA; D'Avila, F; de Geus, EJC; Dedoussis, G; Dimitriou, M; Justice, AE; Döring, A; Eriksson, JG; Farmaki, A-E; Farrall, M; Ferreira, T; Fischer, K; Forouhi, NG; Friedrich, N; Gjesing, AP; Glorioso, N; Kähönen, M; Graff, M; Grallert, H; Grarup, N; Gräßler, J; Grewal, J; Hamsten, A; Harder, MN; Hartman, CA; Hassinen, M; Hastie, N; Karaleftheri, M; Hattersley, AT; Havulinna, AS; Heliövaara, M; Hillege, H; Hofman, A; Holmen, O; Tee Khaw, K; Keinanen-Kiukaanniemi, SM; Kinnunen, L; Knekt, PB; Goel, A; Koistinen, HA; Kolcic, I; Kooner, IK; Koskinen, S; Kovacs, P; Kyriakou, T; Laitinen, T; Langenberg, C; Lewin, AM; Lichtner, P; Gorski, M; Lindgren, CM; Lindström, J; Linneberg, A; Lorbeer, R; Lorentzon, M; Luben, R; Lyssenko, V; Männistö, S; Manunta, P; Leach, IM; Hayward, C; McArdle, WL; Mcknight, B; Mohlke, KL; Mihailov, E; Milani, L; Mills, R; Montasser, ME; Morris, AP; Müller, G; Musk, AW; Heard-Costa, NL; Narisu, N; Ong, KK; Oostra, BA; Osmond, C; Palotie, A; Pankow, JS; Paternoster, L; Penninx, BW; Pichler, I; Pilia, MG; Jackson, AU; Polašek, O; Pramstaller, PP; Raitakari, OT; Rankinen, T; Rao, DC; Rayner, NW; Ribel-Madsen, R; Rice, TK; Richards, M; Ridker, PM; Jokinen, E; Rivadeneira, F; Ryan, KA; Sanna, S; Sarzynski, MA; Scholtens, S; Scott, RA; Sebert, S; Southam, L; Sparsø, TH; Steinthorsdottir, V; Kanoni, S; Stirrups, K

Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/13702

Title:	A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
Authors:	Ried, JS Jeff M, J Chu, AY Bragg-Gresham, JL van Dongen, J Huffman, JE Ahluwalia, TS Cadby, G Eklund, N Eriksson, J Esko, T Stolk, RP Strauch, K Stringham, HM Swertz, MA Swift, AJ Tönjes, A Tsafantakis, E van der Most, PJ Van Vliet-Ostaptchouk, JV Kristiansson, K Homuth, G Vandenput, L Vartiainen, E Venturini, C Verweij, N Viikari, JS Vitart, V Vohl, M-C Vonk, JM Waeber, G Widén, E Hottenga, J-J Kutalik, Z Willemsen, G Wilsgaard, T Winkler, TW Wright, AF Yerges-Armstrong, LM Hua Zhao, J Carola Zillikens, M Boomsma, DI Bouchard, C Hui, J Chambers, JC Lahti, J Chasman, DI Cusi, D Gansevoort, RT Gieger, C Hansen, T Hicks, AA Hu, F Hveem, K Husemoen, LL Jarvelin, M-R Kajantie, E Luan, J Kooner, JS Kuh, D Kuusisto, J Laakso, M Lakka, TA Lehtimäki, T Metspalu, A Hysi, PG Njølstad, I Ohlsson, C Oldehinkel, AJ Mägi, R Palmer, LJ Pedersen, O Perola, M Peters, A Psaty, BM Puolijoki, H Isaacs, A Rauramaa, R Rudan, I Salomaa, V Schwarz, PEH Mahajan, A Shudiner, AR Smit, JH Sørensen, TIA Spector, TD Stefansson, K Ittermann, T Stumvoll, M Tremblay, A Tuomilehto, J Uitterlinden, AG Uusitupa, M Mangino, M Völker, U Vollenweider, P Wareham, NJ Watkins, H Jalilzadeh, S Wilson, JF Zeggini, E Abecasis, GR Boehnke, M Borecki, IB Deloukas, P Medina-Gomez, C van Duijn, CM Fox, C Groop, LC James, AL Heid, IM Hunter, DJ Kaplan, RC McCarthy, MI North, KE O'Connell, JR Schlessinger, D Monda, KL Thorsteinsdottir, U Strachan, DP Jørgensen, T Frayling, T Hirschhorn, JN Müller-Nurasyid, M Loos, RJF Nolte, IM Pérusse, L Prokopenko, I Qi, L Rose, LM Salvi, E Feitosa, MF Smith, MT Snieder, H Stančáková, A Ju Sung, Y Tachmazidou, I Teumer, A Thorleifsson, G van der Harst, P Walker, RW Wang, SR Jousilahti, P Wild, SH Willems, SM Wong, A Zhang, W Albrecht, E Couto Alves, A Bakker, SJL Barlassina, C Bartz, TM Beilby, J Jula, A Bellis, C Bergman, RN Bergmann, S Blangero, J Blüher, M Boerwinkle, E Bonnycastle, LL Bornstein, SR Bruinenberg, M Campbell, H Marie Justesen, J Chen, Y-DI Chiang, CWK Chines, PS Collins, FS Cucca, F Cupples, LA D'Avila, F de Geus, EJC Dedoussis, G Dimitriou, M Justice, AE Döring, A Eriksson, JG Farmaki, A-E Farrall, M Ferreira, T Fischer, K Forouhi, NG Friedrich, N Gjesing, AP Glorioso, N Kähönen, M Graff, M Grallert, H Grarup, N Gräßler, J Grewal, J Hamsten, A Harder, MN Hartman, CA Hassinen, M Hastie, N Karaleftheri, M Hattersley, AT Havulinna, AS Heliövaara, M Hillege, H Hofman, A Holmen, O Tee Khaw, K Keinanen-Kiukaanniemi, SM Kinnunen, L Knekt, PB Goel, A Koistinen, HA Kolcic, I Kooner, IK Koskinen, S Kovacs, P Kyriakou, T Laitinen, T Langenberg, C Lewin, AM Lichtner, P Gorski, M Lindgren, CM Lindström, J Linneberg, A Lorbeer, R Lorentzon, M Luben, R Lyssenko, V Männistö, S Manunta, P Leach, IM Hayward, C McArdle, WL Mcknight, B Mohlke, KL Mihailov, E Milani, L Mills, R Montasser, ME Morris, AP Müller, G Musk, AW Heard-Costa, NL Narisu, N Ong, KK Oostra, BA Osmond, C Palotie, A Pankow, JS Paternoster, L Penninx, BW Pichler, I Pilia, MG Jackson, AU Polašek, O Pramstaller, PP Raitakari, OT Rankinen, T Rao, DC Rayner, NW Ribel-Madsen, R Rice, TK Richards, M Ridker, PM Jokinen, E Rivadeneira, F Ryan, KA Sanna, S Sarzynski, MA Scholtens, S Scott, RA Sebert, S Southam, L Sparsø, TH Steinthorsdottir, V Kanoni, S Stirrups, K
Keywords:	Genome-wide association studies;Statistical methods
Issue Date:	2016
Publisher:	Nature Publishing Group
Citation:	Nature Communications, 7(13357): pp. 1-11, (2016)
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.
URI:	http://bura.brunel.ac.uk/handle/2438/13702
DOI:	http://dx.doi.org/10.1038/ncomms13357
ISSN:	2041-1723
Appears in Collections:	Dept of Mathematics Research Papers

Files in This Item:

File	Description	Size	Format
FullText.pdf		836.49 kB	Adobe PDF	View/Open

Show full item record