Brief research communication - Caught in the trio trap? Potential selection bias inherent to association studies using parent-offspring trios

During the last years, the validity of classic case control studies in psyc hiatric genetic research has been increasingly under question due to the ri sk of population stratification problems inherent to this type of associati on study, By consequence, the application of family-based association studi es using parent-offspring trios has been strongly advocated. Recently, howe ver, in a study comparing clinical characteristics between index patients f rom parent-offspring trios and singleton patients with bipolar affective di sorder, the question was raised whether a systematic neglect of case contro l association studies could lead to a selection bias of susceptibility gene s, In a similar approach, we compared demographic and clinical characterist ics of 122 singleton bipolar patients with those of 54 bipolar patients der ived from parent-offspring trios. The singleton patients did not only prese nt with a higher age of onset, but also with a higher frequency of suicidal behavior and a higher familial loading for suicidality. These findings sug gest that the genetic mechanism for disease might be different between trio -based and classic case control samples, where patients are examined whose parents are not available for genetic studies. Thus, giving up case control designs for the sake of family-based association studies could be at the r isk of selecting against several genetically determined factors. (C) 2001 W iley-Liss,Inc.