Genetic association tests in family samples for multi-category phenotypes

Background Advancements in statistical methods and sequencing technology have led to numerous novel discoveries in human genetics in the past two decades. Among phenotypes of interest, most attention has been given to studying genetic associations with continuous or binary traits. Efficient statistical methods have been proposed and are available for both types of traits under different study designs. However, for multinomial categorical traits in related samples, there is a lack of efficient statistical methods and software. Results We propose an efficient score test to analyze a multinomial trait in family samples, in the context of genome-wide association/sequencing studies. An alternative Wald statistic is also proposed. We also extend the methodology to be applicable to ordinal traits. We performed extensive simulation studies to evaluate the type-I error of the score test, Wald test compared to the multinomial logistic regression for unrelated samples, under different allele frequency and study designs. We also evaluate the power of these methods. Results show that both the score and Wald tests have a well-controlled type-I error rate, but the multinomial logistic regression has an inflated type-I error rate when applied to family samples. We illustrated the application of the score test with an application to the Framingham Heart Study to uncover genetic variants associated with diabesity, a multi-category phenotype. Conclusion Both proposed tests have correct type-I error rate and similar power. However, because the Wald statistics rely on computer-intensive estimation, it is less efficient than the score test in terms of applications to large-scale genetic association studies. We provide computer implementation for both multinomial and ordinal traits.

Problems using ordinal traits with continuous measures of functional diversity

Continuous indices of functional diversity are popular in studies examining community structure and ecosystem function across a wide range of subfields from paleontology to range management. These indices were designed to replace the use of more arbitrary, discrete functional groups or guilds; however, the effect of typical methodological decisions on these new continuous measures has not been fully investigated. To test the effect of using ordinal traits in functional diversity analysis, I first calculated relative functional diversity index values in real plant communities with real continuous trait data and Euclidean distances. I then compared these original values to "treatment" functional diversity index values obtained by discretizing the trait data and using Gower's distance. Agreement between original and treatment values was highly unpredictable and often abysmal. Small methodological choices, such as whether to treat a functional trait as continuous (mm) or ordinal ("small", "medium", "large"), could completely change a perceived functional diversity relationship along an environmental gradient. Some parameter combinations returned results that were no better than random noise. Because simple methodological choices can have such a large impact on continuous functional diversity indices, it is ambiguous whether analyses using ordinal traits are actually measuring an underlying functional diversity relationship between communities or just reflecting the arbitrary parameter choices of researchers.

Genetic association tests in family samples for multi-category phenotypes

Background Advancements in statistical methods and sequencing technology have led to numerous novel discoveries in human genetics in the past two decades. Among phenotypes of interest, most attention has been given to studying genetic associations with continuous or binary traits. Efficient statistical methods have been proposed and are available for both type of traits under different study designs. However, for multinomial categorical traits in related samples, there is a lack of widely used efficient statistical methods and software. Results We propose an efficient score test to analyze a multinomial trait in family samples, in the context of genome-wide association/sequencing studies. An alternative Wald statistic is also proposed. We also extend the methodology to be applicable to ordinal traits. We performed extensive simulation studies to evaluate the type-I error of the score test, Wald test compared to the multinomial logistic regression for unrelated samples, under different allele frequency and study designs. We also evaluate the power of these methods. Results show that both the score and Wald tests have well-controlled type-I error rate, but the multinomial logistic regression has inflated type-I error rate when applied to family samples. We illustrated the application of the score test with an application to the Framingham Heart Study to uncover genetic variants associated with diabesity, a multi-category phenotype. Conclusion Both proposed tests have correct type-I error rate and similar power rate. However, because the Wald statistics rely on computer intensive estimation, it is less efficient than the score test in terms of applications to large-scale genetic association studies. We provide computer implementation for both multinomial and ordinal traits.

Maximum a posteriori Threshold Genomic Prediction Model for Ordinal Traits

Due to the ever-increasing data collected in genomic breeding programs, there is a need for genomic prediction models that can deal better with big data. For this reason, here we propose a Maximum a posteriori Threshold Genomic Prediction (MAPT) model for ordinal traits that is more efficient than the conventional Bayesian Threshold Genomic Prediction model for ordinal traits. The MAPT performs the predictions of the Threshold Genomic Prediction model by using the maximum a posteriori estimation of the parameters, that is, the values of the parameters that maximize the joint posterior density. We compared the prediction performance of the proposed MAPT to the conventional Bayesian Threshold Genomic Prediction model, the multinomial Ridge regression and support vector machine on 8 real data sets. We found that the proposed MAPT was competitive with regard to the multinomial and support vector machine models in terms of prediction performance, and slightly better than the conventional Bayesian Threshold Genomic Prediction model. With regard to the implementation time, we found that in general the MAPT and the support vector machine were the best, while the slowest was the multinomial Ridge regression model. However, it is important to point out that the successful implementation of the proposed MAPT model depends on the informative priors used to avoid underestimation of variance components.

Genomic prediction of ordinal traits via application of the BLASSO and BayesCπ methods in simulated data

This paper aims at evaluating the use of BLASSO and BayesCπ methods for the genomic prediction of ordinal traits, studying factors that influence the performance of the models, and if there is a difference in the ranking of individuals. Genotypic and phenotypic information from a simulated population of 4,100 animals, genotyped by 10k markers (QTL-MAS Workshop) were used. 3,000 animals were used for estimation of the predictive ability and bias accessed through 5-fold cross-validation with five repetitions. The other animals were used as a population of selection. One ANOVA and the Ryan-Einot-Gabriel-Welch test were performed to verify, respectively, which factors influence significantly the genomic prediction and if there is a statistical difference between the models. The results show that the four main factors significantly (p < 0.05) affect the predictive ability of GEBVs (genomic estimated breeding values), and that heritability and the number of categories are the most influential factors. Only for ordinal trait 2, with a density of 9k, significant differences (p < 0.05) were observed between the predictive ability of the methods. In general, the BayesCπ method proved to be more efficient in the identification of relevant SNPs and in the ranking of individuals. Finally, there is a slight superiority of the BayesCπ method for the genomic prediction of ordinal traits.