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Introduction

Most of the common-complex, chronic diseases, that have a high prevalence in our populations, arise through interaction between genetic, environmental and life-style factors. To understand the composite origin of these diseases, we need first to know the path from genotype to phenotype. A complex trait is phenotypically and genetically heterogeneous and thus requires a global genomic approach to understand its etiology and pathogenesis. Such a global approach has not been feasible until recently. So far, all experimental investigations dealt with "single" pieces (eg. genes) of the whole pattern: however relevant the findings, we still lack a broader and comprehensive view of a complex disease per se.

To define a comprehensive genetic epidemiological model of complex traits, we propose to apply new, but already well-established technologies of high throughput genotyping, analyzed with sophisticated statistical-mathematical modelling, to already existing cohorts of subjects with essential hypertension (EH) and intermediate phenotypes of hypertension dependent/associated Target Organ Damages (TOD).

The aim of our integrated approach is to develop an exhaustive model to disentangle the genetic bases of a complex disease using population genetic epidemiology as a methodological tool. We have chosen EH as the disease model, both because of our long-term experience in investigating the genetics of EH and because the cardiovascular complications remain the major cause of death in the EU. Its impact in terms of cost and disability are a devastating burden for patients, for their relatives and for the human potential of the EU. Designing a comprehensive genetic epidemiological model of complex traits will also help us to translate genetic findings into improved diagnostic accuracy and new strategies for early detection, prevention and eventually personalised treatment of a complex trait.

Needless to say, the ultimate goal will be to promote the quality of life of EU populations. For more information, please go to: http://www.hypergenes.eu/


Study team

group photo - Hypergenes launch

Publications

Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Allen HL, Lindgren CM, Luan J, Mägi R,  Randall JC, Vedantam S, Winkler TW, Workalemahu T, Heid IM, Qi L, Steinthorsdottir V, Weedon MN, Wheeler E, Wood AR, Ferreira T, Weyant RJ, Segré AV, Estrada K, Liang L, Nemesh J, Park J-H, Gustafsson S, Kilpeläinen TO, Yang J, Bouatia-Naji N, Esko T, Feitosa MF, Kutalik Z, Mangino M, Rahychaudhuri S, Scherag A, Smith AV, Zhao JH, Aben KK, Amin N, Dixon AL, Fisher E, Glazer NL, Goddard ME, Heard-Costa NL, Hoesel V, Hotteng J-J, Johansson Å, Johnson T, Ketkar S, Lamina C, Li S, Moffatt MF, Myers RH, Narisu N, Perry JRB, Peters MJ, Preuss M, Ripatti S, Rivadeneira F, Sandholt C, Scott LJ, Timpson NJ, TyrerJP, van Wingerden S, Watanabe RM, White CC, Wiklund F, Barlassina C, Chasman DI, Cooper MN, Jansson J-O, Lawrence RW, Pellikka N, Prokopenko I, Shi J, Thiering E, Aben KK, Alavere H, Alibrandi MTS, Almgren P, Arnold AM, Aspelund T, Atwood LD, Balkau B, Balmforth AJ, Bennett AJ, Ben-Shlomo Y, Bergman RN, Bergmann S, Biebermann H, Blakemore AIF, Boes T, Bonnycastle LL, Bornstein SR, Brown MJ, Buchanan TA, Busonero F, Campbell H, Cappuccio FP,  Cavalcanti-Proença C, Chen Y-DI, Chen C-M, Chine PS, Clarke R, Coin L, Connell J, Day INM, den Heijer M, Duan J, Ebrahim S, Elliott P, Elosua R, Eiriksdottir G, Erdo MR, Eriksson JG, Facheri MF, Felix SB, Fischer-Posovszky P, Folsom AR, Friedrich N, Freimer NB, Fu M, Gaget S, Gejman PV, Geus EJC, Gieger C, Gjesing AP, Goel A, Goyette P, Grallert H, Gräßler J, Greenwalt D, Groves CJ, Gudnason V, Guiducci C, Hartikainen A-L, Hassanali N, Hall AS, Havulinna AS, Hayward C, Hengstenberg C, Hicks AA, Hinney A, Hofman A, Homuth G, Hui J, Igl W, Iribarren C, Isomaa B, Jacobs KB, Jarick I, Jewell E, John U, Jørgensen T, Jousilahti P, Jula A, Kaakinen M, Kajanti E, Kaplan LM, Kathiresan S, Kettunen J, Kinnunen L, Knowles JW, Kolcic I, König IR, Koskinen S, Kovacs P, Kuusisto J, Kraft P, Kvaloy L, Laitinen J, Lantieri O, Lanzani C, Launer LJ, Lecoeur C, Lehtimäki T, Lettre T, Liu J, Lokki M-L, Lorentzon M, Luben RN, Ludwig B, MAGIC, Manunta P, Marek D, Marre M, McArdle WL, McCarthy A, McNight B, Meitinger T, Melander O, Meyre D, Midthjell K, Morken MA, Morris AP, Mulic R, Ngwa JS, Nelis M, Neville MJ, O’Donnell CJ, O’Rahilly S, Ong KK, Oostra B, Paré G, Parker AN, Perola M, Pichler I, Piretiläinen KH, Platou CGP, Polasek O, Pouta A, Rafelt S, Raitakari O, Rayner NW, Riddestråle M, Rief W, Ruokonen A, Robertson NR, Rzehak P, Salomaa V, Sander AR, Sandhu MS, Sanna S, Saramies J, Savolainen M, Scherag S, Schipf S, Schreiber S, Schunkert H, Silander K, Sinisalo J, Siscovick DS, Smit JH, Soranzo N, Sovio U, Stephens J, Stringham HM, Surakka I, Swift AJ, Tammesoo M-L, Tardif J-C, Teder-Laving M, Teslovich TM, Thompson JR, Thomson B, Tönjes A, Tuomi T, van Meurs JBJ, van Ommen G-J, Vatin V, Viikari J, Visvikis-Siest S, Vitart V, Vogel CIG, Voight BF, Wallaschofski H, Walters GB, Welch R, Widen E, Wiegand S, Wild SH, Willemsen G, Witte DR, Witteman JC, Xu J, Zhang Q, Zgaga L, Ziegler A, Zitting P, Beilby JP, Farooqi IS, Hebebrand J, Huikuri HV, James AL, Kähönen M, Levinson DF, Macciardi F, Nieminen MS, Ohlsson C, Palmer LJ, Ridker PM, Stumvoll M, Beckmann JS, Boeing H, Boerwinkle E, Boomsma DI, Caulfield MJ, Chanock SJ, Collins FS, Cupples LA, Davey Smith G, Erdmann J, Froguel P, Grönberg H, Gyllensten U, Hall P, Hansen T, Harris TB, Hattersley AT, Haynes RB, Heinrich J, Hu FB, Hveem K, Illig T, Jarvelin M-R, Kaprio J, Karpe F, Khaw K-T, Kiemeney L, Krude H, Laakso M, Lawlor DA, Metspalu A, Munroe PB, Ouwehand WH, Pedersen O, Penninx BW, Peters A, Pramstaller PP, Quertemous T, Reinehr T, Rissanen A, Rudan I, Samani NJ, Schwarz PEH, Shuldiner AR, Spector TD, Tuomilehto J, Uda M, Uitterlinden A, Valle TT, Wabitsch M, Waeber G, Wareham NJ, Watkins H on behalf of Procardis Consortium, Wilson JF, Wright AF, Zilliken MC, Chatterjee N, McCarroll SA, Purcell S, Schadt EE, Visscher PM, Assimes TL, Borecki IB, Deloukas P, Fox CS, Groop LC, Haritunian T, Hunter DJ, Kaplan RC, Mohlke KL, O’Connell JR, Peltonen L, Schlessinger D, Strachan DP, van Duijn CM, Wichmann E-E, Frayling TM, Thorsteindottir U, Abecasis GR, Barroso I, Boehnke M, Stefansson K, North KE, McCarthy MI, Hirschhorn JN, Ingelsson E and Loos RJF. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genetics 2010; 42(11): 937-48