Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Meta-analysis of Mendelian randomization studies incorporating all three genotypes
AU - Palmer, Tom M.
AU - Thompson, John R.
AU - Tobin, Martin D.
N1 - Copyright 2008 John Wiley & Sons, Ltd.
PY - 2008/12/30
Y1 - 2008/12/30
N2 - In Mendelian randomization a carefully selected gene is used as an instrumental variable in the estimation of the association between a biological phenotype and a disease. A study using Mendelian randomization will have information on an individual's disease status, the genotype and the phenotype. The phenotype must be on the causal pathway between gene and disease for the instrumental-variable analysis to be valid. For a biallelic polymorphism there are three possible genotypes with which to compare disease risk. Existing methods select two of the three possible genotypes for use in a Mendelian randomization analysis. Multivariate meta-analysis models for Mendelian randomization case-control studies are proposed, which extend previous methods by estimating the pooled phenotype-disease association across both genotype comparisons by using the gene-disease log odds ratios and differences in mean phenotypes. The methods are illustrated using a meta-analysis of the effect of a gene related to collagen production on bone mineral density and osteoporotic fracture.
AB - In Mendelian randomization a carefully selected gene is used as an instrumental variable in the estimation of the association between a biological phenotype and a disease. A study using Mendelian randomization will have information on an individual's disease status, the genotype and the phenotype. The phenotype must be on the causal pathway between gene and disease for the instrumental-variable analysis to be valid. For a biallelic polymorphism there are three possible genotypes with which to compare disease risk. Existing methods select two of the three possible genotypes for use in a Mendelian randomization analysis. Multivariate meta-analysis models for Mendelian randomization case-control studies are proposed, which extend previous methods by estimating the pooled phenotype-disease association across both genotype comparisons by using the gene-disease log odds ratios and differences in mean phenotypes. The methods are illustrated using a meta-analysis of the effect of a gene related to collagen production on bone mineral density and osteoporotic fracture.
KW - Bone Density
KW - Case-Control Studies
KW - Collagen Type I
KW - Genotype
KW - Humans
KW - Meta-Analysis as Topic
KW - Models, Genetic
KW - Models, Statistical
KW - Osteoporosis
KW - Phenotype
KW - Polymorphism, Genetic
KW - Random Allocation
KW - Risk
U2 - 10.1002/sim.3423
DO - 10.1002/sim.3423
M3 - Journal article
C2 - 18767201
VL - 27
SP - 6570
EP - 6582
JO - Statistics in Medicine
JF - Statistics in Medicine
SN - 0277-6715
IS - 30
ER -