Meta-analysis of genetic studies using Mendelian randomization--a multivariate approach.

@article{citeulike:2997938, abstract = {In traditional epidemiological studies the association between phenotype (risk factor) and disease is often biased by confounding and reverse causation. As a person's genotype is assigned by a seemingly random process, genes are potentially useful instrumental variables for adjusting for such bias. This type of adjustment combines information on the genotype-disease association and the genotype-phenotype association to estimate the phenotype-disease association and has become known as Mendelian randomization. The information on genotype-disease and genotype-phenotype may well come from a meta-analysis. In such a synthesis, a multivariate approach needs to be used whenever some studies provide evidence on both the genotype-phenotype and genotype-disease associations. This paper presents two multivariate meta-analytical models, which differ in their treatment of the heterogeneities (between-study variances). Heterogeneities on the genotype-phenotype and genotype-disease associations may be highly correlated, but a multivariate model that parameterizes the heterogeneity directly is difficult to fit because that correlation is poorly estimated. We advocate an alternative model that treats the heterogeneities on genotype-phenotype and phenotype-disease as being independent. This model fits readily and implicitly defines the correlation between the heterogeneities on genotype-phenotype and genotype-disease. We show how either maximum likelihood or a Bayesian approach with vague prior distributions can be used to fit the alternative model.}, address = {Department of Health Sciences, Centre for Biostatistics and Genetic Epidemiology, University of Leicester, 22-28 Princess Rd West, Leicester, LE1 6TP, U.K. john.thompson@le.ac.uk}, author = {Thompson, J. R. and Minelli, C. and Abrams, K. R. and Tobin, M. D. and Riley, R. D. }, citeulike-article-id = {2997938}, doi = {http://dx.doi.org/10.1002/sim.2100}, issn = {0277-6715}, journal = {Statistics in medicine}, keywords = {mendelian, meta-analysis}, month = {July}, number = {14}, pages = {2241--2254}, posted-at = {2008-07-14 05:20:48}, priority = {2}, title = {Meta-analysis of genetic studies using Mendelian randomization--a multivariate approach.}, url = {http://dx.doi.org/10.1002/sim.2100}, volume = {24}, year = {2005} }

TY - JOUR ID - citeulike:2997938 L3 - citeulike-article-id:2997938 TI - Meta-analysis of genetic studies using Mendelian randomization--a multivariate approach. JF - Statistics in medicine VL - 24 IS - 14 SP - 2241 EP - 2254 AD - Department of Health Sciences, Centre for Biostatistics and Genetic Epidemiology, University of Leicester, 22-28 Princess Rd West, Leicester, LE1 6TP, U.K. john.thompson@le.ac.uk SN - 0277-6715 N2 - In traditional epidemiological studies the association between phenotype (risk factor) and disease is often biased by confounding and reverse causation. As a person's genotype is assigned by a seemingly random process, genes are potentially useful instrumental variables for adjusting for such bias. This type of adjustment combines information on the genotype-disease association and the genotype-phenotype association to estimate the phenotype-disease association and has become known as Mendelian randomization. The information on genotype-disease and genotype-phenotype may well come from a meta-analysis. In such a synthesis, a multivariate approach needs to be used whenever some studies provide evidence on both the genotype-phenotype and genotype-disease associations. This paper presents two multivariate meta-analytical models, which differ in their treatment of the heterogeneities (between-study variances). Heterogeneities on the genotype-phenotype and genotype-disease associations may be highly correlated, but a multivariate model that parameterizes the heterogeneity directly is difficult to fit because that correlation is poorly estimated. We advocate an alternative model that treats the heterogeneities on genotype-phenotype and phenotype-disease as being independent. This model fits readily and implicitly defines the correlation between the heterogeneities on genotype-phenotype and genotype-disease. We show how either maximum likelihood or a Bayesian approach with vague prior distributions can be used to fit the alternative model. KW - mendelian KW - meta-analysis AU - Thompson, JR AU - Minelli, C AU - Abrams, KR AU - Tobin, MD AU - Riley, RD PY - 2005/07/30/ UR - http://dx.doi.org/10.1002/sim.2100 ER -