SP 2

Central patient resource and bridging between genotype and phenotype

Schizophrenia (SCZ), bipolar disorder (BD), and unipolar affective disorder (MD) are heterogeneous and highly heritable disorders. Since the etiology of these disorders remains unclear, no biologically valid classification system is available, and no biomarker has yet been identified to assist in diagnosis or the prediction of disease course. Instead, psychiatric diagnoses are assigned on the basis of symptom check-lists, a minimum duration and number of clinically observable symptoms. As a result, patients with the same diagnosis can differ widely in terms of both their particular constellation of clinical symptoms and their disease course. Furthermore, the applied clinical criteria overlap on both the clinical and – as previously demonstrated by our group – the molecular genetic level.
The overarching aim of subproject 2 (SP2) is to facilitate the development of a biologically guided classification system for SCZ, BD, and MD by identifying robust genotype-phenotype associations, and obtaining insights into etiology. To achieve this, SP2 pursues three goals:

1.) Systematic analyses of genotype-phenotype associations in large samples of patients, both within and across currently applied diagnostic boundaries. This work is performed in close collaboration with other SPs from the Consortium, in particular SP1, SP3, SP4, SP5, and SP6.

2.) The provision and extension of a central patient resource for the IntegraMent Consortium. The availability of large and well characterized samples is a prerequisite for the work of SP2, SP3, SP4, SP5, SP6, SP9, and SP10. The samples provided by the SP2 central platform are among the largest of their type worldwide. These samples are being continually expanded, and subjected in part to longitudinal follow up. Phenotype characterization includes the assessment of clinical symptoms; endophenotypes, such as cognitive functioning; disease course; pharmacoresponse (see Figure); and environmental influences.

3.) Consolidation and expansion of this sample through the involvement of other German clinical psychiatry centers from beyond the Consortium. This is being supported by the German Society for Psychiatry, Psychotherapy, and Psychosomatics (DGPPN-cohort), through an initiative established by SP2.

Results of a pharmacogenetic GWAS of lithium response in BD patients. (Hou et al. 2016) Reprinted with permission from Elsevier (The Lancet, March 2016, Volume 387, Pages 1085-1093). © https://www.sciencedirect.com/science/article/pii/S0140673616001434