Multilocus Bayesian Meta-Analysis of Gene-Disease Associations

被引：22

作者：

Newcombe, Paul J. ^{[1
]}

Verzilli, Claudio ^{[1
]}

Casas, Juan P. ^{[1
]}

Hingorani, Aroon D. ^{[2
]}

Smeeth, Liam ^{[1
]}

Whittaker, John C. ^{[1
]}

机构：

[1] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England

[2] UCL, Ctr Clin Pharmacol, London WC1E 6JJ, England

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2009年 / 84卷 / 05期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; PHOSPHODIESTERASE; 4D; ISCHEMIC-STROKE; PDE4D GENE; POLYMORPHISMS; RISK;

D O I：

10.1016/j.ajhg.2009.04.001

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Meta-analysis is a vital tool in genetic epidemiology. However, meta-analyses to identify gene-disease associations are compromised when contributing studies have typed partially overlapping sets of markers. Currently, only marginal analyses are possible, and these are restricted to the subset of studies typing that marker. This does not allow full use of available data and leads to the confounding of marker effects by closely associated markers. We present a Bayesian approach that exploits prior information on underlying haplotypes to allow multi-marker analysis incorporating data from all relevant studies of a gene or region, irrespective of the markers typed. We present results from application of our approach to data on a possible association between PDE4D and ischemic stroke.

引用

页码：567 / 580

页数：14

共 26 条

[1] 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

[2] Variation in the PDE4D gene and ischemic stroke risk - A systematic review and meta-analysis on 5200 cases and 6600 controls [J].

Bevan, Steve ;

Dichgans, Martin ;

Gschwendtner, Andreas ;

Kuhlenbaeumer, Gregor ;

Ringelstein, E. B. ;

Markus, Hugh S. .

STROKE, 2008, 39 (07) :1966-1971

[3]

Bishop Y.M., 2007, Discrete Multivariate Analysis: Theory and Practice

[4] Association of phosphodiesterase 4D polymorphisms with ischemic stroke in a US population stratified by hypertension status [J].

Brophy, VH ;

Ro, SK ;

Rhees, BK ;

Lui, LY ;

Lee, JM ;

Umblas, N ;

Bentley, LG ;

Li, J ;

Cheng, S ;

Browner, WS ;

Erlich, HA .

STROKE, 2006, 37 (06) :1385-1390

[5] Association study designs for complex diseases [J].

Cardon, LR ;

Bell, JI .

NATURE REVIEWS GENETICS, 2001, 2 (02) :91-99

[6] Epidemiological methods for studying genes and environmental factors in complex diseases [J].

Clayton, D ;

McKeigue, PM .

LANCET, 2001, 358 (9290) :1356-1360

[7] Problems of reporting genetic associations with complex outcomes [J].

Colhoun, HM ;

McKeigue, PM ;

Smith, GD .

LANCET, 2003, 361 (9360) :865-872

[8]

GILKS W, 1996, PRACTICE

[9]

Green PJ, 1995, BIOMETRIKA, V82, P711, DOI 10.2307/2337340

[10] The gene encoding phosphodiesterase 4D confers risk of ischemic stroke [J].

Gretarsdottir, S ;

Thorleifsson, G ;

Reynisdottir, ST ;

Manolescu, A ;

Jonsdottir, S ;

Jonsdottir, T ;

Gudmundsdottir, T ;

Bjarnadottir, SM ;

Einarsson, OB ;

Gudjonsdottir, HM ;

Hawkins, M ;

Gudmundsson, G ;

Gudmundsdottir, H ;

Andrason, H ;

Gudmundsdottir, AS ;

Sigurdardottir, M ;

Chou, TT ;

Nahmias, J ;

Goss, S ;

Sveinbjörnsdottir, S ;

Valdimarsson, EM ;

Jakobsson, F ;

Agnarsson, U ;

Gudnason, V ;

Thorgeirsson, G ;

Fingerle, J ;

Gurney, M ;

Gudbjartsson, D ;

Frigge, ML ;

Kong, A ;

Stefansson, K ;

Gulcher, JR .

NATURE GENETICS, 2003, 35 (02) :131-138

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