Title | Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Berndt, SI, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, MF, Justice, AE, Monda, KL, Croteau-Chonka, DC, Day, FR, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, AU, Luan, J'an, Randall, JC, Vedantam, S, Willer, CJ, Winkler, TW, Wood, AR, Workalemahu, T, Hu, Y-J, Lee, SHong, Liang, L, Lin, D-Y, Min, JL, Neale, BM, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg-Gresham, JL, Cadby, G, Heijer, Mden, Eklund, N, Fischer, K, Goel, A, Hottenga, J-J, Huffman, JE, Jarick, I, Johansson, A, Johnson, T, Kanoni, S, Kleber, ME, König, IR, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, McArdle, WL, Medina-Gómez, C, Müller-Nurasyid, M, Ngwa, JS, Nolte, IM, Paternoster, L, Pechlivanis, S, Perola, M, Peters, MJ, Preuss, M, Rose, LM, Shi, J, Shungin, D, Smith, AVernon, Strawbridge, RJ, Surakka, I, Teumer, A, Trip, MD, Tyrer, J, van Vliet-Ostaptchouk, JV, Vandenput, L, Waite, LL, Zhao, JH, Absher, D, Asselbergs, FW, Atalay, M, Attwood, AP, Balmforth, AJ, Basart, H, Beilby, J, Bonnycastle, LL, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de Faire, U, de Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, DM, Farrall, M, Ferrario, MM, Ferrieres, J, Franke, L, Frau, F, Gejman, PV, Grallert, H, Grönberg, H, Gudnason, V, Hall, AS, Hall, P, Hartikainen, A-L, Hayward, C, Heard-Costa, NL, Heath, AC, Hebebrand, J, Homuth, G, Hu, FB, Hunt, SE, Hyppönen, E, Iribarren, C, Jacobs, KB, Jansson, J-O, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K-T, Kivimaki, M, Koenig, W, Kraja, AT, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, JH, Lakka, TA, Langenberg, C, Launer, LJ, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M-L, Lorentzon, M, Madden, PA, Magnusson, PK, Manunta, P, Marek, D, März, W, Leach, IMateo, McKnight, B, Medland, SE, Mihailov, E, Milani, L, Montgomery, GW, Mooser, V, Mühleisen, TW, Munroe, PB, Musk, AW, Narisu, N, Navis, G, Nicholson, G, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CNA, Palotie, A, Peden, JF, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, PP, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, TE, Sambrook, JG, Sanders, AR, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S-Y, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, JC, Stirrups, K, Stolk, RP, Stumvoll, M, Swift, AJ, Theodoraki, EV, Thorand, B, Trégouët, D-A, Tremoli, E, van der Klauw, MM, van Meurs, JBJ, Vermeulen, SH, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widen, E, Wild, SH, Willemsen, G, Winkelmann, BR, Witteman, JCM, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zillikens, CM, Amouyel, P, Boehm, BO, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, AL, Cusi, D, Dedoussis, GV, Erdmann, J, Eriksson, JG, Franks, PW, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, TB, Hengstenberg, C, Hicks, AA, Hingorani, A, Hinney, A, Hofman, A, Hovingh, KG, Hveem, K, Illig, T, Jarvelin, M-R, Jöckel, K-H, Keinanen-Kiukaanniemi, SM, Kiemeney, LA, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, DF, Martin, NG, Metspalu, A, Morris, AD, Nieminen, MS, Njølstad, I, Ohlsson, C, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Penninx, B, Power, C, Province, MA, Psaty, BM, Qi, L, Rauramaa, R, Ridker, PM, Ripatti, S, Salomaa, V, Samani, NJ, Snieder, H, Sørensen, TIA, Spector, TD, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, AG, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, NJ, Watkins, H, Wichmann, H-E, Wilson, JF, Abecasis, GR, Assimes, TL, Barroso, I, Boehnke, M, Borecki, IB, Deloukas, P, Fox, CS, Frayling, T, Groop, LC, Haritunian, T, Heid, IM, Hunter, D, Kaplan, RC, Karpe, F, Moffatt, MF, Mohlke, KL, O'Connell, JR, Pawitan, Y, Schadt, EE, Schlessinger, D, Steinthorsdottir, V, Strachan, DP, Thorsteinsdottir, U, van Duijn, CM, Visscher, PM, Di Blasio, AMaria, Hirschhorn, JN, Lindgren, CM, Morris, AP, Meyre, D, Scherag, A, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJF, Ingelsson, E |
Journal | Nat Genet |
Volume | 45 |
Issue | 5 |
Pagination | 501-12 |
Date Published | 2013 May |
ISSN | 1546-1718 |
Keywords | Anthropometry, Body Height, Body Mass Index, Case-Control Studies, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Obesity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Waist-Hip Ratio |
Abstract | <p>Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.</p> |
DOI | 10.1038/ng.2606 |
Alternate Journal | Nat. Genet. |
PubMed ID | 23563607 |
PubMed Central ID | PMC3973018 |
Grant List | R01 CA082659 / CA / NCI NIH HHS / United States CZB/4/710 / / Chief Scientist Office / United Kingdom G9521010 / / Medical Research Council / United Kingdom 098017 / / Wellcome Trust / United Kingdom RP-PG-0310-1002 / / Department of Health / United Kingdom K05 AA017688 / AA / NIAAA NIH HHS / United States U01 HG007416 / HG / NHGRI NIH HHS / United States T32 GM074905 / GM / NIGMS NIH HHS / United States R01 DK072193 / DK / NIDDK NIH HHS / United States / / Medical Research Council / United Kingdom G1000143 / / Medical Research Council / United Kingdom R01 DK075787 / DK / NIDDK NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States MC_U106179471 / / Medical Research Council / United Kingdom 097117 / / Wellcome Trust / United Kingdom MC_UU_12015/2 / / Medical Research Council / United Kingdom MC_U123092720 / / Medical Research Council / United Kingdom 14136 / / Cancer Research UK / United Kingdom / / Cancer Research UK / United Kingdom MC_U106179472 / / Medical Research Council / United Kingdom G1002084 / / Medical Research Council / United Kingdom G0401527 / / Medical Research Council / United Kingdom 090532 / / Wellcome Trust / United Kingdom MR/K006584/1 / / Medical Research Council / United Kingdom P30 DK020572 / DK / NIDDK NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States MC_U106188470 / / Medical Research Council / United Kingdom G0601261 / / Medical Research Council / United Kingdom G0600237 / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom MC_U105260558 / / Medical Research Council / United Kingdom |