Bayesian trio models for association in the presence of genotyping errors.
Errors in genotyping can greatly affect family-based association studies. If a mendelian inconsistency is detected, the family is usually removed from the analysis. This reduces power, and may introduce bias. In addition, a large proportion of genotyping errors remain undetected, and these also reduce power. We present a Bayesian framework for performing association studies with SNP data on samples of trios consisting of parents with an affected offspring, while allowing for the presence of both detectable and undetectable genotyping errors. This framework also allows for the inclusion of missing genotypes. Associations between the SNP and disease were modelled in terms of the genotypic relative risks. The performances of the analysis methods were investigated under a variety of models for disease association and genotype error, looking at both power to detect association and precision of genotypic relative risk estimates. As expected, power to detect association decreased as genotyping error probability increased. Importantly, however, analyses allowing for genotyping error had similar power to standard analyses when applied to data without genotyping error. Furthermore, allowing for genotyping error yielded relative risk estimates that were approximately unbiased, together with 95% credible intervals giving approximately correct coverage. The methods were also applied to a real dataset: a sample of schizophrenia cases and their parents genotyped at SNPs in the dysbindin gene. The analysis methods presented here require no prior information on the genotyping error probabilities, and may be fitted in WinBUGS.
Bernardinelli
L
L
MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom.
Berzuini
C
C
Seaman
S
S
Holmans
P
P
D000483:Alleles; D001499:Bayes Theorem; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008962:Models, Theoretical; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015983:Selection Bias