Common vs. rare allele hypotheses for complex diseases

被引:439
作者
Schork, Nicholas J. [1 ]
Murray, Sarah S.
Frazer, Kelly A.
Topol, Eric J.
机构
[1] Scripps Res Inst, Scripps Translat Sci Inst, La Jolla, CA 92037 USA
关键词
PLASMA-LEVELS; VARIANTS; SEQUENCE; ASSOCIATION; MUTATIONS; PATHWAYS; GENES; SUSCEPTIBILITY; CONTRIBUTE; DIVERSITY;
D O I
10.1016/j.gde.2009.04.010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
There has been growing debate over the nature of the genetic contribution to individual susceptibility to common complex diseases such as diabetes, osteoporosis, and cancer. The 'Common Disease, Common Variant (CDCV)' hypothesis argues that genetic variations with appreciable frequency in the population at large, but relatively low 'penetrance' (or the probability that a carrier of the relevant variants will express the disease), are the major contributors to genetic susceptibility to common diseases. The 'Common Disease, Rare Variant (CDRV)' hypothesis, on the contrary, argues that multiple rare DNA sequence variations, each with relatively high penetrance, are the major contributors to genetic susceptibility to common diseases. Both hypotheses have their place in current research efforts.
引用
收藏
页码:212 / 219
页数:8
相关论文
共 48 条
[1]   Medical sequencing at the extremes of human body mass [J].
Ahituv, Nadav ;
Kavaslar, Nihan ;
Schackwitz, Wendy ;
Ustaszewska, Anna ;
Martin, Joel ;
Hebert, Sybil ;
Doelle, Heather ;
Ersoy, Baran ;
Kryukov, Gregory ;
Schmidt, Steffen ;
Yosef, Nir ;
Ruppin, Eytan ;
Sharan, Roded ;
Vaisse, Christian ;
Sunyaev, Shamil ;
Dent, Robert ;
Cohen, Jonathan ;
McPherson, Ruth ;
Pennacchio, Len A. .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (04) :779-791
[2]   Multiple rare nonsynonymous variants in the Adenomatous Polyposis Coli gene predispose to colorectal adenomas [J].
Azzopardi, Duncan ;
Dallosso, Anthony R. ;
Eliason, Kristilyn ;
Hendrickson, Brant C. ;
Jones, Natalie ;
Rawstorne, Edward ;
Colley, James ;
Moskvina, Valentina ;
Frye, Cynthia ;
Sampson, Julian R. ;
Wenstrup, Richard ;
Scholl, Thomas ;
Cheadle, Jeremy P. .
CANCER RESEARCH, 2008, 68 (02) :358-363
[3]   Cystic fibrosis: A worldwide analysis of CFTR mutations - Correlation with incidence data and application to screening [J].
Bobadilla, JL ;
Macek, M ;
Fine, JP ;
Farrell, PM .
HUMAN MUTATION, 2002, 19 (06) :575-606
[4]   Common and rare variants in multifactorial susceptibility to common diseases [J].
Bodmer, Walter ;
Bonilla, Carolina .
NATURE GENETICS, 2008, 40 (06) :695-701
[5]   Replicating genotype-phenotype associations [J].
Chanock, Stephen J. ;
Manolio, Teri ;
Boehnke, Michael ;
Boerwinkle, Eric ;
Hunter, David J. ;
Thomas, Gilles ;
Hirschhorn, Joel N. ;
Abecasis, Goncalo ;
Altshuler, David ;
Bailey-Wilson, Joan E. ;
Brooks, Lisa D. ;
Cardon, Lon R. ;
Daly, Mark ;
Donnelly, Peter ;
Fraumeni, Joseph F., Jr. ;
Freimer, Nelson B. ;
Gerhard, Daniela S. ;
Gunter, Chris ;
Guttmacher, Alan E. ;
Guyer, Mark S. ;
Harris, Emily L. ;
Hoh, Josephine ;
Hoover, Robert ;
Kong, C. Augustine ;
Merikangas, Kathleen R. ;
Morton, Cynthia C. ;
Palmer, Lyle J. ;
Phimister, Elizabeth G. ;
Rice, John P. ;
Roberts, Jerry ;
Rotimi, Charles ;
Tucker, Margaret A. ;
Vogan, Kyle J. ;
Wacholder, Sholom ;
Wijsman, Ellen M. ;
Winn, Deborah M. ;
Collins, Francis S. .
NATURE, 2007, 447 (7145) :655-660
[6]   Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].
Chin, L. ;
Meyerson, M. ;
Aldape, K. ;
Bigner, D. ;
Mikkelsen, T. ;
VandenBerg, S. ;
Kahn, A. ;
Penny, R. ;
Ferguson, M. L. ;
Gerhard, D. S. ;
Getz, G. ;
Brennan, C. ;
Taylor, B. S. ;
Winckler, W. ;
Park, P. ;
Ladanyi, M. ;
Hoadley, K. A. ;
Verhaak, R. G. W. ;
Hayes, D. N. ;
Spellman, Paul T. ;
Absher, D. ;
Weir, B. A. ;
Ding, L. ;
Wheeler, D. ;
Lawrence, M. S. ;
Cibulskis, K. ;
Mardis, E. ;
Zhang, Jinghui ;
Wilson, R. K. ;
Donehower, L. ;
Wheeler, D. A. ;
Purdom, E. ;
Wallis, J. ;
Laird, P. W. ;
Herman, J. G. ;
Schuebel, K. E. ;
Weisenberger, D. J. ;
Baylin, S. B. ;
Schultz, N. ;
Yao, Jun ;
Wiedemeyer, R. ;
Weinstein, J. ;
Sander, C. ;
Gibbs, R. A. ;
Gray, J. ;
Kucherlapati, R. ;
Lander, E. S. ;
Myers, R. M. ;
Perou, C. M. ;
McLendon, Roger .
NATURE, 2008, 455 (7216) :1061-1068
[7]   Low LDL cholesterol in African Americans resulting from frequent nonsense mutations in PCSK9 [J].
Cohen, J ;
Pertsemlidis, A ;
Kotowski, IK ;
Graham, R ;
Garcia, CK ;
Hobbs, HH .
NATURE GENETICS, 2005, 37 (03) :328-328
[8]   Sequence variations in PCSK9, low LDL, and protection against coronary heart disease [J].
Cohen, JC ;
Boerwinkle, E ;
Mosley, TH ;
Hobbs, HH .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (12) :1264-1272
[9]   Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels [J].
Cohen, JC ;
Pertsemlidis, A ;
Fahmi, S ;
Esmail, S ;
Vega, GL ;
Grundy, SM ;
Hobbs, HH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (06) :1810-1815
[10]   Multiple rare Alleles contribute to low plasma levels of HDL cholesterol [J].
Cohen, JC ;
Kiss, RS ;
Pertsemlidis, A ;
Marcel, YL ;
McPherson, R ;
Hobbs, HH .
SCIENCE, 2004, 305 (5685) :869-872