No evidence for phenotypic variation between probands in case‐control versus family‐based association studies of schizophrenia

Abstract

Traditional case-control genetic association studies utilizing unrelated probands are often used interchangeably with family-based designs to detect genes for complex psychiatric disorders. This strategy may be limited, however, if significant phenotypic variation exists between probands enrolled in these two types of studies. The present study compared 37 probands enrolled in a case-control study of schizophrenia with 37 age-, sex-, and ethnically matched probands enrolled in a family-based study of schizophrenia. Age of onset of illness was compared as well as performance on a battery of cognitive tests assessing attention, working memory, executive function, and verbal memory. Results revealed no significant differences in age of onset between the two groups or on any measure of cognitive performance. These data do not support reports of significant phenotypic variation between probands in case-control and family-based studies, and suggest that studies utilizing family-based approaches may be used to replicate reports of association made with case-control designs in schizophrenia.

Positron Emission Tomography in Schizophrenia: A New Perspective

“…Evidence from linkage studies favors disrupted-in-schizophrenia-1 (30,31), neuregulin-1 (32,33), and dysbindin (34,35) as the most promising candidate genes for schizophrenia (36). Some neurochemical genes associated with dopamine regulation, such as the catechol-O-methyltransferase (COMT) gene (37,38), have been associated with performance during prefrontal-mediated working memory tasks (39)(40)(41)(42)(43). Several genes are involved in other neurotransmitter pathways.…”

Is there a phenotypic difference between probands in case‐control versus family‐based association studies?

“…Malhotra et al [2002] argue that our finding might be due merely to the fact that we did not match our two groups for factors like age at interview or gender. However, they do not mention that we performed a logistic regression analysis to control for age at interview, duration of disease, and gender.…”

“…Recently, Malhotra et al [2002] investigated whether probands from case‐control (CCPs) and family‐based association studies (FBPs) of schizophrenia differed in phenotypic features. We thank the authors for their attempt to address our recent finding on this issue in a large sample of patients with bipolar affective disorder [Schulze et al, 2001].…”

Family factors and sampling approach differentially influence attention deficit/hyperactivity disorder subtypes

“…Singleton-trio differences were not observed for schizophrenia probands. 5 Following a similar logic, West et al 1 tested whether ADHD probands ascertained from clinics differed on whether one or both parents had participated in DNA collection. They found that compared to children from trios, children from duos showed a significantly higher frequency of DSM-IV combined subtype ADHD and comorbid conduct disorder as well as more conduct disorder symptoms.…”