Trend Tests While Considering Genotype Uncertainty

Genome-wide association research is an effective method to study the association between disease and genes.The genetic markers of DNA samples are used to screen out the causative genes of complex genetic diseases.The Cochran-Armitage trend test method,as a genotype-based trend test method,is often used to evaluate the association between a binary classification variable and an ordered classification variable.Sasieni(1997)has previously demonstrated in the literature that in case-control design-based gene association studies,the genotype-based hypothesis testing method has a more robust advantage than the allele-based hypothesis testing method,because in HardyWeinberg The trend test method based on genotype is still applicable under the condition that the lattice balance law is not established,but the chi-square test method based on alleles has low efficiency and poor applicability.Therefore,this article chooses the Cochran-Armitage trend test method to study the association between disease and genes.In the past,most gene association studies were based on known genetic models,but for most complex genetic diseases,its genetic model is unknown.If the genetic model is unknown,directly assuming a specific genetic model may cause test statistics.The reduction in efficacy leads to unsatisfactory inspection results.Secondly,due to technical factors or limitations of research costs,deviations may occur in the genetic marker typing of genes,resulting in the genotype of some samples being missing,and the genotype of the sample cannot be completely determined,and the wrong filling genotype will also This will reduce the power of inspection statistics and affect the effectiveness of inspection.This paper considers constructing trend test statistics in case of missing genotypes and unknown genetic models to solve the problems of missing genotypes or unknown genetic models in gene association studies.In this paper,the sample data of individual genotype probability is simulated under different genotype uncertainty rate parameters.For these genotype probability sample data,CochranArmitage under dominant genetic model,additive genetic model and recessive genetic model are proposed respectively.Trend test statistics,and more robust test statistics through the MAX3 test method.The MAX3 test statistic is more robust than the Cochran-Armitage trend test statistic when the genetic model is unknown.At the same time,a simple algorithm is proposed to calculate the approximate distribution of the MAX3 test statistic under the original hypothesis,which simplifies the calculation complexity.According to the simulation results in this paper,under various parameters,the first error rate of the MAX3 test statistic is generally small,and the statistical power is relatively stable under each genetic model.In summary,in the case of uncertain genotypes,the MAX3 test statistic is a robust statistic in the case of unknown genetic models.