Advancing the Genetics of Lewy Body Disorders with Disease‐Modifying Treatments in Mind. Issue 4 (19th August 2022)

• Record Type: Journal Article
• Authors: Levy, Gilberto; Levin, Bruce; Engelhardt, Eliasz
• Is Part Of: Advanced genetics. Volume 3:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-19
• Subjects: dementia with Lewy bodies -- disease‐modifying treatments -- genetics -- Lewy body disorders -- Parkinson's disease; Genetics -- Periodicals; Genomics -- Periodicals; Genomics; Genetics; Genetics; Genomics; Electronic journals; Periodicals; 576.5
• DOI: 10.1002/ggn2.202200011
• Languages: English
• ISSNs: 2641-6573

Abstract

Abstract: In this article, a caveat for advancing the genetics of Lewy body disorders is raised, given the nosological controversy about whether to consider dementia with Lewy bodies (DLB) and Parkinson's disease (PD) as one entity or two separate entities. Using the framework of the sufficient and component causes model of causation, as further developed into an evolution‐based model of causation, it is proposed that a disease of complex etiology is defined as having a relatively high degree of sharing of the component causes (a genetic or environmental factor), that is, a low degree of heterogeneity of the sufficient causes. Based on this definition, only if the sharing of component causes within each of two diseases is similar to their combined sharing can lumping be warranted. However, it is not known whether the separate and combined sharing are similar before conducting the etiologic studies. This means that lumping DLB and PD can be counterproductive as it can decrease the ability to detect component causes despite the potential benefit of conducting studies with larger sample sizes. In turn, this is relevant to the development of disease‐modifying treatments, because non‐overlapping causal genetic factors may result in distinct pathogenetic pathways providing promising targets for interventions. Abstract : Lewy body disorders include two of the most common neurodegenerative diseases, dementia with Lewy bodies and Parkinson's disease. While major progress has been made in uncovering the genetic etiology of these diseases, this article argues, for the sake of discovering disease‐modifying treatments, that they should continue to be studied separately rather than combined in genetic studies.