The KI Psychiatric Genomics Institute (KI-PGI) is a systematic program established to evaluate the epidemiological, molecular, and cellular effects of genetic risk loci for psychiatric disorders, such as schizophrenia and depression.
KI-PGI is located at the Department of Medical Epidemiology and Biostatistics (MEB) at Karolinska Institutet. The director of KI-PGI is Professor Patrick Sullivan and co-director is Principal Researcher Lu Yi.
Genetic studies of psychiatric disorders have achieved unprecedented advances and have become one of the most fast-paced areas in human genetics. During the last decade, there has been exceptional progress in understanding the genetic architecture of psychiatric disorders. Today hundreds of specific genetic risk variants for psychiatric disorders such as schizophrenia have been identified using comprehensive genome-wide genetic data in large cohorts of patients and controls, in combination with rigorous statistical methods.
The KI-PGI has a focus on both identifying new genetic risk variants, understanding the genetic underpinnings in subsets of patients for example based on treatment resistance, as well as elucidating the implications for patients, clinicians, and neuroscientists. Some of the overarching goals of the KI-PGI are: how do genes and environment act and interact to modify risk for severe psychiatric disorders (e.g., schizophrenia, severe major depressive disorder)?
By what molecular and cellular mechanisms do these genes act? We have data from large case-control studies of schizophrenia (including the Swedish Schizophrenia Study (S3)), and all subjects have been comprehensively evaluated with genome-wide SNP arrays, analysis of copy number variants (CNVs), and whole exome and whole genome sequencing, as well as comprehensive national health register data. We are also working on major data sets for severe major depression and an eﬀort to harmonize psychiatric genomics and national register data in Denmark, Norway, and Sweden (TRYGGVE2).
Prof. Sullivan leads the worldwide collaboration of Psychiatric Genomics Consortium (PGC), which is one of the most innovative and productive research efforts in the history of psychiatry. All efforts are deeply collaborative, and in addition to the 150+ institutions involved in the PGC, the KI-PGI actively work with 10 major genetic, psychiatric, neuroscience, and functional genomics groups. We have established, long term collaborations within the KI, Sweden, Europe, the US, and Australia. We have multiple large new datasets. These recent papers describe some of our eﬀorts in psychiatric genomics (Nguyen et al, Mol Psychiatry 2022), functional genomics, identiﬁcation of brain cell types for schizophrenia (initial study and replication) (Skene et al, Nat. Genet. 2018 and Bryois et al, Nat. Genet. 2020), the work of the PGC, and reviews for the ﬁeld (Sullivan and Geschwind, Cell 2019).
The major funder for the KI-Psychiatric Genomics Institute (KI-PGI) is the Swedish research council (Vetenskapsrådet) (grant no 583-2013-8865). Additional funding comes from the EU (the COSYN project, H2020 grant no. 667301; the CoMorMent project H2020 grant no. 847776; and the REALMENT project H2020 grant no. 964874), and NIMH (The Swedish schizophrenia study - S3, grant no. R01 MH077139-07 RPPR; the Trans-Nordic Study of Extreme Major Depression, grant no. R01 MH123724).
Genetic heterogeneity and subtypes of major depression.
Nguyen TD, Harder A, Xiong Y, Kowalec K, Hägg S, Cai N, Kuja-Halkola R, Dalman C, Sullivan PF, Lu Y
Mol Psychiatry 2022 Mar;27(3):1667-1675
Genetic identification of brain cell types underlying schizophrenia.
Skene NG, Bryois J, Bakken TE, Breen G, Crowley JJ, Gaspar HA, Giusti-Rodriguez P, Hodge RD, Miller JA, Muñoz-Manchado AB, O'Donovan MC, Owen MJ, Pardiñas AF, Ryge J, Walters JTR, Linnarsson S, Lein ES, , Sullivan PF, Hjerling-Leffler J
Nat Genet 2018 Jun;50(6):825-833
Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease.
Bryois J, Skene NG, Hansen TF, Kogelman LJA, Watson HJ, Liu Z, , , , Brueggeman L, Breen G, Bulik CM, Arenas E, Hjerling-Leffler J, Sullivan PF
Nat Genet 2020 May;52(5):482-493
Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders.
Sullivan PF, Geschwind DH
Cell 2019 Mar;177(1):162-183