Statistical adjustment of genotyping error in a case-control study of childhood leukaemia

Genotyping has become more cost-effective and less invasive with the use of buccal cell sampling. However, low or fragmented DNA yields from buccal cells collected using FTA cards often requires additional whole genome amplification to produce sufficient DNA for genotyping. In our case-control study...

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Bibliographic Details
Published in:	BMC medical research methodology 2012-09, Vol.12 (1), p.141-141, Article 141
Main Authors:	Cooper, Matthew N, de Klerk, Nicholas H, Greenop, Kathryn R, Jamieson, Sarra E, Anderson, Denise, van Bockxmeer, Frank M, Armstrong, Bruce K, Milne, Elizabeth
Format:	Article
Language:	eng
Subjects:	Adjustment Analysis Bias Biostatistics Cancer Case-Control Studies Child Deoxyribonucleic acid Diagnosis Diagnostic Errors DNA DNA - analysis DNA - genetics DNA - isolation & purification DNA Fingerprinting - methods DNA repair DNA sequencing Female Genetic aspects Genetic screening Genetic testing Genetic Variation Genetics Genomes Genomics Genotype Genotype & phenotype Genotyping Techniques Hospitals Humans Leukemia - diagnosis Leukemia - genetics Leukemia in children Male Measurement error Medical research Methods Nucleotide sequencing Quality control Reagent Kits, Diagnostic Statistical methods Studies Technical Advance Whole genome amplification
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Summary:	Genotyping has become more cost-effective and less invasive with the use of buccal cell sampling. However, low or fragmented DNA yields from buccal cells collected using FTA cards often requires additional whole genome amplification to produce sufficient DNA for genotyping. In our case-control study of childhood leukaemia, discordance was found between genotypes derived from blood and whole genome amplified FTA buccal DNA samples. We aimed to develop a user-friendly method to correct for this genotype misclassification, as existing methods were not suitable for use in our study. Discordance between the results of blood and buccal-derived DNA was assessed in childhood leukaemia cases who had both blood and FTA buccal samples. A method based on applying misclassification probabilities to measured data and combining results using multiple imputations, was devised to correct for error in the genotypes of control subjects, for whom only buccal samples were available, to minimize bias in the odds ratios in the case-control analysis. Application of the correction method to synthetic datasets showed it was effective in producing correct odds ratios from data with known misclassification. Moreover, when applied to each of six bi-allelic loci, correction altered the odds ratios in the logically anticipated manner given the degree and direction of the misclassification revealed by the investigations in cases. The precision of the effect estimates decreased with decreasing size of the misclassification data set. Bias arising from differential genotype misclassification can be reduced by correcting results using this method whenever data on concordance of genotyping results with those from a different and probably better DNA source are available.
ISSN:	1471-2288 1471-2288