Dr. Olli Pietiläinen, PhD is a group leader and senior scientist at the Neuroscience Center of the Helsinki Institute of Life Science at the University of Helsinki and a visiting researcher at the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT. He is also an affiliate senior scientist at the Institute for Molecular Medicine Finland (FIMM). Olli received his doctorate in molecular Genetics at University of Helsinki (PI Aarno Palotie) and trained as a postdoctoral fellow at Harvard University with Professor Kevin Eggan specializing in genomics of iPSC-derived neuronal models.

An expert in complex disease genetics and functional genomics, Olli Pietiläinen is co-leading patient sample collections in Finland including the Northern Finnish Intellectual Disability study and SUPER biomarker study.  His research focuses on understanding the genetic basis and biological mechanisms underlying severe psychiatric and neurodevelopmental disorders. For this purpose, he combines genetic analysis, genomic readouts and molecular cell biology in human induced pluripotent stem cell-derived models of disease-relevant huma cell types.

Using multimodal, longitudinal data to explore clinical impact of genetic variants in psychotic disorders

Schizophrenia and other psychotic disorders are severely debilitating disorders with high heritability. They share many underlying genetic factors and clinical symptoms. Therefore, the diagnostic separation is not always clear-cut. The identified genetic variants contributing to the susceptibility involves hundreds of common variants with small effects, copy number variations (CNVs), and ultra rare coding variants with outsized effect sizes. But less is known how these variants affect disease-courses of individuals with psychotic disorders. Rare coding variants are attractive for biological modelling, but whether they differ in the disease course from idiopathic, polygenic forms of the disorders remains to be characterized. To address these questions, we study disease course trajectories in conjunction with genetic data of individuals with psychotic disorders in the SUPER-Finland study (n=10,403). The SUPER study was incorporated into the nation-wide FinnGen Biobank study (n=520,000) with genetic and longitudinal electronic health record (EHR) data with decades of follow-up. By tracking the past disease courses, we identify distinct effects for polygenic scores and rare coding variants influencing the disease courses, treatment trajectories and hospitalization, as well as cognitive performance. Screening sequencing data revealed over 130 carriers with ultra rare protein truncating variants (PTVs) in genes nominated by the Schizophrenia Exome Sequencing Consortium (SCHEMA) in schizophrenia. Analysing longitudinal data provided a more comprehensive view of the clinical implications and disease course associated with the rare PTVs associated with schizophrenia.  Our results highlight the utility of diverse, multimodal longitudinal data in studying genetic influences in psychotic disorders.