1. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
- Author
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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, Randall JC, Vedantam S, Willer CJ, Winkler TW, Wood AR, Workalemahu T, Hu YJ, Lee SH, Liang L, Lin DY, Min JL, Neale BM, Thorleifsson G, Yang J, Albrecht E, Amin N, Bragg-Gresham JL, Cadby G, den Heijer M, Eklund N, Fischer K, Goel A, Hottenga JJ, Huffman JE, Jarick I, Johansson Å, Johnson T, Kanoni S, Kleber ME, König IR, Kristiansson K, Kutalik Z, Lamina C, Lecoeur C, Li G, Mangino M, McArdle WL, Medina-Gomez 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 AV, 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, Ferrières J, Franke L, Frau F, Gejman PV, Grallert H, Grönberg H, Gudnason V, Hall AS, Hall P, Hartikainen AL, Hayward C, Heard-Costa NL, Heath AC, Hebebrand J, Homuth G, Hu FB, Hunt SE, Hyppönen E, Iribarren C, Jacobs KB, Jansson JO, Jula A, Kähönen M, Kathiresan S, Kee F, Khaw KT, Kivimäki 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 ML, Lorentzon M, Madden PA, Magnusson PK, Manunta P, Marek D, März W, Mateo Leach I, 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 CN, 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 SY, 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, Tregouet DA, Tremoli E, Van der Klauw MM, van Meurs JB, Vermeulen SH, Viikari J, Virtamo J, Vitart V, Waeber G, Wang Z, Widén E, Wild SH, Willemsen G, Winkelmann BR, Witteman JC, Wolffenbuttel BH, Wong A, Wright AF, Zillikens MC, Amouyel P, Boehm BO, Boerwinkle E, Boomsma DI, Caulfield MJ, Chanock SJ, Cupples LA, 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 MR, Jöckel KH, 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 TI, 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 HE, 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 AM, Hirschhorn JN, Lindgren CM, Morris AP, Meyre D, Scherag A, McCarthy MI, Speliotes EK, North KE, Loos RJ, and Ingelsson E
- Subjects
- Body Mass Index, Case-Control Studies, Genotype, Humans, Meta-Analysis as Topic, Phenotype, Waist-Hip Ratio, White People genetics, Anthropometry, Body Height genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Obesity genetics, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci
- Abstract
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.
- Published
- 2013
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