Bayesian meta-analysis of genetic association studies with different sets of markers.

@article{citeulike:2983407, abstract = {Robust assessment of genetic effects on quantitative traits or complex-disease risk requires synthesis of evidence from multiple studies. Frequently, studies have genotyped partially overlapping sets of SNPs within a gene or region of interest, hampering attempts to combine all the available data. By using the example of C-reactive protein (CRP) as a quantitative trait, we show how linkage disequilibrium in and around its gene facilitates use of Bayesian hierarchical models to integrate informative data from all available genetic association studies of this trait, irrespective of the SNP typed. A variable selection scheme, followed by contextualization of SNPs exhibiting independent associations within the haplotype structure of the gene, enhanced our ability to infer likely causal variants in this region with population-scale data. This strategy, based on data from a literature based systematic review and substantial new genotyping, facilitated the most comprehensive evaluation to date of the role of variants governing CRP levels, providing important information on the minimal subset of SNPs necessary for comprehensive evaluation of the likely causal relevance of elevated CRP levels for coronary-heart-disease risk by Mendelian randomization. The same method could be applied to evidence synthesis of other quantitative traits, whenever the typed SNPs vary among studies, and to assist fine mapping of causal variants.}, address = {Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.}, author = {Verzilli, C. and Shah, T. and Casas, J. P. and Chapman, J. and Sandhu, M. and Debenham, S. L. and Boekholdt, M. S. and Khaw, K. T. and Wareham, N. J. and Judson, R. and Benjamin, E. J. and Kathiresan, S. and Larson, M. G. and Rong, J. and Sofat, R. and Humphries, S. E. and Smeeth, L. and Cavalleri, G. and Whittaker, J. C. and Hingorani, A. D. }, citeulike-article-id = {2983407}, doi = {http://dx.doi.org/10.1016/j.ajhg.2008.01.016}, issn = {1537-6605}, journal = {American journal of human genetics}, keywords = {association, bayes, meta-analysis}, month = {April}, number = {4}, pages = {859--872}, posted-at = {2008-07-10 11:36:25}, priority = {2}, title = {Bayesian meta-analysis of genetic association studies with different sets of markers.}, url = {http://dx.doi.org/10.1016/j.ajhg.2008.01.016}, volume = {82}, year = {2008} }

TY - JOUR ID - citeulike:2983407 L3 - citeulike-article-id:2983407 TI - Bayesian meta-analysis of genetic association studies with different sets of markers. JF - American journal of human genetics VL - 82 IS - 4 SP - 859 EP - 872 AD - Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. SN - 1537-6605 N2 - Robust assessment of genetic effects on quantitative traits or complex-disease risk requires synthesis of evidence from multiple studies. Frequently, studies have genotyped partially overlapping sets of SNPs within a gene or region of interest, hampering attempts to combine all the available data. By using the example of C-reactive protein (CRP) as a quantitative trait, we show how linkage disequilibrium in and around its gene facilitates use of Bayesian hierarchical models to integrate informative data from all available genetic association studies of this trait, irrespective of the SNP typed. A variable selection scheme, followed by contextualization of SNPs exhibiting independent associations within the haplotype structure of the gene, enhanced our ability to infer likely causal variants in this region with population-scale data. This strategy, based on data from a literature based systematic review and substantial new genotyping, facilitated the most comprehensive evaluation to date of the role of variants governing CRP levels, providing important information on the minimal subset of SNPs necessary for comprehensive evaluation of the likely causal relevance of elevated CRP levels for coronary-heart-disease risk by Mendelian randomization. The same method could be applied to evidence synthesis of other quantitative traits, whenever the typed SNPs vary among studies, and to assist fine mapping of causal variants. KW - association KW - bayes KW - meta-analysis AU - Verzilli, C AU - Shah, T AU - Casas, JP AU - Chapman, J AU - Sandhu, M AU - Debenham, SL AU - Boekholdt, MS AU - Khaw, KT AU - Wareham, NJ AU - Judson, R AU - Benjamin, EJ AU - Kathiresan, S AU - Larson, MG AU - Rong, J AU - Sofat, R AU - Humphries, SE AU - Smeeth, L AU - Cavalleri, G AU - Whittaker, JC AU - Hingorani, AD PY - 2008/04// UR - http://dx.doi.org/10.1016/j.ajhg.2008.01.016 ER -