Validation of PHASE for deriving N-acetyltransferase 2 haplotypes in the Western Cape mixed ancestry population

Background There is a shortage of data on the accuracy of statistical methods for the prediction of N-acetyltransferase 2 (NAT2) haplotypes in the mixed ancestry population of the Western Cape. Objective This study aimed to identify the NAT2 haplotypes and assess the accuracy of PHASE version 2.1.1 in assigning NAT2 haplotypes to a mixed ancestry population from the Western Cape. Methods This study was conducted between 2013 and 2016. The NAT2 gene was amplified and sequenced from the DNA of 100 self-identified mixed ancestry participants. Haplotyping was performed by molecular and computational techniques. Agreement was assessed between the two techniques. Results Haplotypes were assigned to 93 samples, of which 67 (72%) were ambiguous. Haplotype prediction by PHASE demonstrated 94.6% agreement (kappa 0.94, p T, c.622T>C, c.809T>C and c.387C>T) were detected. Conclusion PHASE accurately predicted the phenotype in 92 of 93 samples (99%) from genotypic data in our mixed ancestry sample population, and is therefore a suitable alternative to molecular methods to individualise isoniazid therapy in this high burden tuberculosis setting.