Advantages of mixed effects models over traditional ANOVA models in developmental studies: a worked example in a mouse model of fetal alcohol syndrome.
Developmental studies in animals often violate the assumption of statistical independence of observations due to the hierarchical nature of the data (i.e., pups cluster by litter, correlation of individual observations over time). Mixed effect modeling (MEM) provides a robust analytical approach for addressing problems associated with hierarchical data. This article compares the application of MEM to traditional ANOVA models within the context of a developmental study of prenatal ethanol exposure in mice. The results of the MEM analyses supported the ANOVA results in showing that a large proportion of the variability in both behavioral score and brain weight could be explained by ethanol. The MEM also identified that there were significant interactions between ethanol and litter size in relation to behavioral scores and brain weight. In addition, the longitudinal modeling approach using linear MEM allowed us to model for flexible weight gain over time, as well as to provide precise estimates of these effects, which would be difficult in repeated measures ANOVA.
Wainwright
Patricia E
PE
Department of Health Studies and Gerontology, University of Waterloo, 200 University Avenue W, Waterloo, Ontario N2L 3G1, Canada. wainwrig@healthy.uwaterloo.ca
Leatherdale
Scott T
ST
Dubin
Joel A
JA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015982:Bias; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008098:Litter Size; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015233:Models, Statistical; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism; D012737:Sex Factors
D011453:Prostaglandins; D000431:Ethanol; D007213:Indomethacin