A bias-ed assessment of the use of SNPs in human complex traits

被引:77
作者
Terwilliger, JD
Haghighi, F
Hiekkalinna, TS
Göring, HH
机构
[1] Columbia Univ, Dept Psychiat, New York, NY 10032 USA
[2] New York State Psychiat Inst & Hosp, Columbia Genome Ctr, Div Mol Genet, New York, NY 10032 USA
[3] Natl Publ Hlth Inst, Dept Mol Med, FIN-00251 Helsinki, Finland
[4] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA
关键词
D O I
10.1016/S0959-437X(02)00357-X
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Although many biotechnological advancements have been made in the past decade, there has been very limited success in unraveling the genetic component of complex traits. Heavily invested research has been initiated based on etiological models of unrealistic simplicity and conducted under poor experimental designs, on data sets of insufficient size, leading to an overestimation of the effect sizes of genetic variants and the quantity and quality of linkage disequilibrium (LD). Arguments about whether families or unrelated individuals provide more power for gene mapping have been erroneously debated as issues of whether linkage or LD are more detectable sorts of correlation. Although the latter issue may be subject to debate, there is no doubt that family-based analysis is more powerful for detecting linkage and/or LD. If the recent advances in biotechnology are to be exploited effectively, vastly improved study designs will be imperative, as the reasons for the lack of success to date have much more to do with biology than technology, an issue that has become increasingly clear with the findings of the past years.
引用
收藏
页码:726 / 734
页数:9
相关论文
共 69 条
[1]   Bias in estimates of quantitative-trait-locus effect in genome scans: Demonstration of the phenomenon and a method-of-moments procedure for reducing bias [J].
Allison, DB ;
Fernandez, JR ;
Heo, M ;
Zhu, SK ;
Etzel, C ;
Beasley, TM ;
Amos, CI .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (03) :575-585
[2]   Rethinking genetic strategies to study complex diseases [J].
Brookes, AJ .
TRENDS IN MOLECULAR MEDICINE, 2001, 7 (11) :512-516
[3]   Association study designs for complex diseases [J].
Cardon, LR ;
Bell, JI .
NATURE REVIEWS GENETICS, 2001, 2 (02) :91-99
[4]   Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase [J].
Clark, AG ;
Weiss, KM ;
Nickerson, DA ;
Taylor, SL ;
Buchanan, A ;
Stengård, J ;
Salomaa, V ;
Vartiainen, E ;
Perola, M ;
Boerwinkle, E ;
Sing, CF .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 63 (02) :595-612
[5]   A NEW 5-YEAR PLAN FOR THE UNITED-STATES HUMAN GENOME PROJECT [J].
COLLINS, F ;
GALAS, D .
SCIENCE, 1993, 262 (5130) :43-46
[6]   Implications of the Human Genome Project for medical science [J].
Collins, FS ;
McKusick, VA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (05) :540-544
[7]   Variations on a theme: Cataloging human DNA sequence variation [J].
Collins, FS ;
Guyer, MS ;
Chakravarti, A .
SCIENCE, 1997, 278 (5343) :1580-1581
[8]  
Collins FS, 2001, CANCER, V91, P221, DOI 10.1002/1097-0142(20010101)91:1+<221::AID-CNCR8>3.3.CO
[9]  
2-0
[10]   New goals for the US Human Genome Project: 1998-2003 [J].
Collins, FS ;
Patrinos, A ;
Jordan, E ;
Chakravarti, A ;
Gesteland, R ;
Walters, L ;
Fearon, E ;
Hartwelt, L ;
Langley, CH ;
Mathies, RA ;
Olson, M ;
Pawson, AJ ;
Pollard, T ;
Williamson, A ;
Wold, B ;
Buetow, K ;
Branscomb, E ;
Capecchi, M ;
Church, G ;
Garner, H ;
Gibbs, RA ;
Hawkins, T ;
Hodgson, K ;
Knotek, M ;
Meisler, M ;
Rubin, GM ;
Smith, LM ;
Smith, RF ;
Westerfield, M ;
Clayton, EW ;
Fisher, NL ;
Lerman, CE ;
McInerney, JD ;
Nebo, W ;
Press, N ;
Valle, D .
SCIENCE, 1998, 282 (5389) :682-689