Common disorders are quantitative traits

被引:512
作者
Plomin, Robert [1 ]
Haworth, Claire M. A. [1 ]
Davis, Oliver S. P. [1 ]
机构
[1] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
GENOME-WIDE ASSOCIATION; GENETIC RISK; SUSCEPTIBILITY LOCI; BREAST-CANCER; CROHN-DISEASE; PREDICTION; VARIANT; PATHOGENESIS; CHALLENGES; PHENOTYPE;
D O I
10.1038/nrg2670
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
After drifting apart for 100 years, the two worlds of genetics quantitative genetics and molecular genetics - are finally coming together in genome-wide association (GWA) research, which shows that the heritability of complex traits and common disorders is due to multiple genes of small effect size. We highlight a polygenic framework, supported by recent GWA research, in which qualitative disorders can be interpreted simply as being the extremes of quantitative dimensions. Research that focuses on quantitative traits including the low and high ends of normal distributions - could have far-reaching implications for the diagnosis, treatment and prevention of the problematic extremes of these traits.
引用
收藏
页码:872 / 878
页数:7
相关论文
共 49 条
[1]   Five common gene variants identify elevated genetic risk for coronary heart disease [J].
Bare, Lance A. ;
Morrison, Alanna C. ;
Rowland, Charles M. ;
Shiffman, Dov ;
Luke, May M. ;
Iakoubova, Olga A. ;
Kane, John P. ;
Malloy, Mary J. ;
Ellis, Stephen G. ;
Pankow, James S. ;
Willerson, James T. ;
Devlin, James J. ;
Boerwinkle, Eric .
GENETICS IN MEDICINE, 2007, 9 (10) :682-689
[2]   Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].
Barrett, Jeffrey C. ;
Hansoul, Sarah ;
Nicolae, Dan L. ;
Cho, Judy H. ;
Duerr, Richard H. ;
Rioux, John D. ;
Brant, Steven R. ;
Silverberg, Mark S. ;
Taylor, Kent D. ;
Barmada, M. Michael ;
Bitton, Alain ;
Dassopoulos, Themistocles ;
Datta, Lisa Wu ;
Green, Todd ;
Griffiths, Anne M. ;
Kistner, Emily O. ;
Murtha, Michael T. ;
Regueiro, Miguel D. ;
Rotter, Jerome I. ;
Schumm, L. Philip ;
Steinhart, A. Hillary ;
Targan, Stephan R. ;
Xavier, Ramnik J. ;
Libioulle, Cecile ;
Sandor, Cynthia ;
Lathrop, Mark ;
Belaiche, Jacques ;
Dewit, Olivier ;
Gut, Ivo ;
Heath, Simon ;
Laukens, Debby ;
Mni, Myriam ;
Rutgeerts, Paul ;
Van Gossum, Andre ;
Zelenika, Diana ;
Franchimont, Denis ;
Hugot, Jean-Pierre ;
de Vos, Martine ;
Vermeire, Severine ;
Louis, Edouard ;
Cardon, Lon R. ;
Anderson, Carl A. ;
Drummond, Hazel ;
Nimmo, Elaine ;
Ahmad, Tariq ;
Prescott, Natalie J. ;
Onnie, Clive M. ;
Fisher, Sheila A. ;
Marchini, Jonathan ;
Ghori, Jilur .
NATURE GENETICS, 2008, 40 (08) :955-962
[3]   PHENOMICS: THE SYSTEMATIC STUDY OF PHENOTYPES ON A GENOME-WIDE SCALE [J].
Bilder, R. M. ;
Sabb, F. W. ;
Cannon, T. D. ;
London, E. D. ;
Jentsch, J. D. ;
Parker, D. Stott ;
Poldrack, R. A. ;
Evans, C. ;
Freimer, N. B. .
NEUROSCIENCE, 2009, 164 (01) :30-42
[4]   A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels [J].
Bouatia-Naji, Nabila ;
Rocheleau, Ghislain ;
Van Lommel, Leentje ;
Lemaire, Katleen ;
Schuit, Frans ;
Cavalcanti-Proenca, Christine ;
Marchand, Marion ;
Hartikainen, Anna-Liisa ;
Sovio, Ulla ;
De Graeve, Franck ;
Rung, Johan ;
Vaxillaire, Martine ;
Tichet, Jean ;
Marre, Michel ;
Balkau, Beverley ;
Weill, Jacques ;
Elliott, Paul ;
Jarvelin, Marjo-Riitta ;
Meyre, David ;
Polychronakos, Constantin ;
Dina, Christian ;
Sladek, Robert ;
Froguel, Philippe .
SCIENCE, 2008, 320 (5879) :1085-1088
[5]   Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].
Burton, Paul R. ;
Clayton, David G. ;
Cardon, Lon R. ;
Craddock, Nick ;
Deloukas, Panos ;
Duncanson, Audrey ;
Kwiatkowski, Dominic P. ;
McCarthy, Mark I. ;
Ouwehand, Willem H. ;
Samani, Nilesh J. ;
Todd, John A. ;
Donnelly, Peter ;
Barrett, Jeffrey C. ;
Davison, Dan ;
Easton, Doug ;
Evans, David ;
Leung, Hin-Tak ;
Marchini, Jonathan L. ;
Morris, Andrew P. ;
Spencer, Chris C. A. ;
Tobin, Martin D. ;
Attwood, Antony P. ;
Boorman, James P. ;
Cant, Barbara ;
Everson, Ursula ;
Hussey, Judith M. ;
Jolley, Jennifer D. ;
Knight, Alexandra S. ;
Koch, Kerstin ;
Meech, Elizabeth ;
Nutland, Sarah ;
Prowse, Christopher V. ;
Stevens, Helen E. ;
Taylor, Niall C. ;
Walters, Graham R. ;
Walker, Neil M. ;
Watkins, Nicholas A. ;
Winzer, Thilo ;
Jones, Richard W. ;
McArdle, Wendy L. ;
Ring, Susan M. ;
Strachan, David P. ;
Pembrey, Marcus ;
Breen, Gerome ;
St Clair, David ;
Caesar, Sian ;
Gordon-Smith, Katherine ;
Jones, Lisa ;
Fraser, Christine ;
Green, Elain K. .
NATURE, 2007, 447 (7145) :661-678
[6]   Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases [J].
Chamaillard, M ;
Philpott, D ;
Girardin, SE ;
Zouali, H ;
Lesage, S ;
Chareyre, F ;
Bui, TH ;
Giovannini, M ;
Zaehringer, U ;
Penard-Lacronique, V ;
Sansonetti, PJ ;
Hugot, JP ;
Thomas, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (06) :3455-3460
[7]   A framework for interpreting genome-wide association studies of psychiatric disorders The Psychiatric GWAS Consortium Steering Committee [J].
Cichon, Sven ;
Craddock, Nick ;
Daly, Mark ;
Faraone, Stephen V. ;
Gejman, Pablo V. ;
Kelsoe, John ;
Lehner, Thomas ;
Levinson, Douglas F. ;
Moran, Audra ;
Sklar, Pamela ;
Sullivan, Patrick F. .
MOLECULAR PSYCHIATRY, 2009, 14 (01) :10-17
[8]   Progress and challenges in genome-wide association studies in humans [J].
Donnelly, Peter .
NATURE, 2008, 456 (7223) :728-731
[9]   Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: A metaanalysis [J].
Economou, M ;
Trikalinos, TA ;
Loizou, KT ;
Tsianos, EV ;
Ioannidis, JPA .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2004, 99 (12) :2393-2404
[10]   Genetic Loci Associated With C-Reactive Protein Levels and Risk of Coronary Heart Disease [J].
Elliott, Paul ;
Chambers, John C. ;
Zhang, Weihua ;
Clarke, Robert ;
Hopewell, Jemma C. ;
Peden, John F. ;
Erdmann, Jeanette ;
Braund, Peter ;
Engert, James C. ;
Bennett, Derrick ;
Coin, Lachlan ;
Ashby, Deborah ;
Tzoulaki, Ioanna ;
Brown, Ian J. ;
Mt-Isa, Shahrul ;
McCarthy, Mark I. ;
Peltonen, Leena ;
Freimer, Nelson B. ;
Farrall, Martin ;
Ruokonen, Aimo ;
Hamsten, Anders ;
Lim, Noha ;
Froguel, Philippe ;
Waterworth, Dawn M. ;
Vollenweider, Peter ;
Waeber, Gerard ;
Jarvelin, Marjo-Riitta ;
Mooser, Vincent ;
Scott, James ;
Hall, Alistair S. ;
Schunkert, Heribert ;
Anand, Sonia S. ;
Collins, Rory ;
Samani, Nilesh J. ;
Watkins, Hugh ;
Kooner, Jaspal S. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 302 (01) :37-48