title: Control groups in paediatric epilepsy research: do first-degree cousins show familial effects?
abstract: To determine whether first-degree cousins of children with idiopathic focal and genetic generalized epilepsies show any association across measures of cognition, behaviour, and brain structure. The presence/absence of associations addresses the question of whether and to what extent first-degree cousins may serve as unbiased controls in research addressing the cognitive, psychiatric, and neuroimaging features of paediatric epilepsies. Participants were children (aged 8-18) with epilepsy who had at least one first-degree cousin control enrolled in the study (n=37) and all enrolled cousin controls (n=100). Participants underwent neuropsychological assessment and brain imaging (cortical, subcortical, and cerebellar volumes), and parents completed the Child Behaviour Checklist (CBCL). Data (based on 42 outcome measures) from cousin controls were regressed on the corresponding epilepsy cognitive, behavioural, and imaging measures in a linear mixed model and case/control correlations were examined. Of the 42 uncorrected correlations involving cognitive, behavioural, and neuroimaging measures, only two were significant (p<0.05). The median correlation was 0.06. A test for whether the distribution of p values deviated from the null distribution under no association was not significant (p>0.25). Similar results held for the cognition/behaviour and brain imaging measures separately. Given the lack of association between cases and first-degree cousin performances on measures of cognition, behaviour, and neuroimaging, the results suggest a non-significant genetic influence on control group performance. First-degree cousins appear to be unbiased controls for cognitive, behavioural, and neuroimaging research in paediatric epilepsy.
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hanson
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Blaise
authors.initials: B
authors.lastname: Morrison
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Jana E
authors.initials: JE
authors.lastname: Jones
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Daren C
authors.initials: DC
authors.lastname: Jackson
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Dace
authors.initials: D
authors.lastname: Almane
authors.affiliation: Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL.
authors.forename: Michael
authors.initials: M
authors.lastname: Seidenberg
authors.affiliation: Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rathouz
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Hermann
mesh_terms: D000293:Adolescent; D002648:Child; D035061:Control Groups; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000235:genetics; D004829:Epilepsy, Generalized / Q000175:diagnosis* / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male
keywords: behaviour; brain imaging; cognition; cousin control; focal idiopathic epilepsy; genetic generalized epilepsy; research design