Computational protocol: Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects

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Protocol publication

[…] During the quality control procedure, genotype call rates per sample and per polymorphism < 80% were excluded from the analysis. The outcome measures of treatment with MPH were evaluated as quantitative data according to CGI-S and CGAS. Analyses of the effects of different genotypes on response to treatment over time were performed using linear mixed-effects models. These mixed-models are useful for repeated-measures analyses where follow-up times are not uniform across all subjects. Models were constructed using the lme function from the nlme package in R.As in other genetically complex diseases in which the model of inheritance is uncertain, the analyses were performed under the assumption of dominant, recessive, codominant, and additive models. The best model was selected based on the one with the lowest Akaike information criterion (AIC). Data for variants located on chromosome X (HTR2C and STS genes) were analyzed taking X inactivation into account according to Clayton’s approach.Age, sex, ADHD subtype, previous treatment, type of MPH (immediate-release vs. extended-release/both formulations), and dosage were also entered into the models as potential explanatory covariates. Statistical significance for main effects and interactions was assessed using the ANOVA F-test and set at a 2-tailed p value of 0.05. In these multivariable models, the effect size of the associations was measured by the coefficients of the models “β”.The proportion of the variance explained by the model was assessed using Omega Squared. […]

Pipeline specifications

Software tools lme4, nlme
Application Mathematical modeling