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A polygenic resilience score moderates the genetic risk for schizophrenia
- Source :
- Hess, J L, Tylee, D S, Mattheisen, M, Børglum, A D, Als, T D, Grove, J, Werge, T, Mortensen, P B, Mors, O, Nordentoft, M, Hougaard, D M, Byberg-Grauholm, J, Bækvad-Hansen, M, Greenwood, T A, Tsuang, M T, Curtis, D, Steinberg, S, Sigurdsson, E, Stefánsson, H, Stefánsson, K, Edenberg, H J, Holmans, P, Faraone, S V, Glatt, S J, Schizophrenia Working Group of the Psychiatric Genomics Consortium & Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) 2021, ' A polygenic resilience score moderates the genetic risk for schizophrenia ', Molecular Psychiatry, vol. 26, no. 3, pp. 800-815 . https://doi.org/10.1038/s41380-019-0463-8, Schizophrenia Working Group of the Psychiatric Genomics Consortium 2019, ' A polygenic resilience score moderates the genetic risk for schizophrenia ', Molecular Psychiatry . https://doi.org/10.1038/s41380-019-0463-8, Molecular psychiatry 26, 800–815 (2021). doi:10.1038/s41380-019-0463-8, Molecular psychiatry, Molecular psychiatry, 26, 800-815. Nature Publishing Group, Hess, J L, Tylee, D S, Mattheisen, M, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum, A D, Als, T D, Grove, J, Werge, T, Mortensen, P B, Mors, O, Nordentoft, M, Hougaard, D M, Byberg-Grauholm, J, Bækvad-Hansen, M, Greenwood, T A, Tsuang, M T, Curtis, D, Steinberg, S, Sigurdsson, E, Stefánsson, H, Stefánsson, K, Edenberg, H J, Holmans, P, Faraone, S V & Glatt, S J 2021, ' A polygenic resilience score moderates the genetic risk for schizophrenia ', Molecular Psychiatry, vol. 26, no. 3, pp. 800–815 . https://doi.org/10.1038/s41380-019-0463-8, Molecular psychiatry, vol 26, iss 3, Hess, J L, Tylee, D S, Mattheisen, M, The Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum, A D, Als, T D, Grove, J, Werge, T, Mortensen, P B, Mors, O, Nordentoft, M, Hougaard, D M, Byberg-grauholm, J, Bækvad-hansen, M, Greenwood, T A, Tsuang, M T, Curtis, D, Steinberg, S, Sigurdsson, E, Stefánsson, H, Stefánsson, K, Edenberg, H J, Holmans, P, Faraone, S V & Glatt, S J 2021, ' A polygenic resilience score moderates the genetic risk for schizophrenia ', Molecular Psychiatry, vol. 26, pp. 800–815 . https://doi.org/10.1038/s41380-019-0463-8, Molecular Psychiatry, 26(3), 800-815. Nature Publishing Group
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Publisher's version (útgefin grein)<br />Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.<br />SJG is supported by grants from the U.S. National Institutes of Health (5R01MH101519, 5R01AG054002), the Sidney R. Baer, Jr. Foundation, and NARSAD: The Brain & Behavior Research Foundation. SVF is supported by the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement number 602805, the European Union’s Horizon 2020 research and innovation programme under grant agreement number 667302 and NIMH grants 5R01MH101519 and U01 MH109536-01. HJE is supported by grants from the U.S. National Institutes of Health (U10 AA008401; U01 MH109532). Statistical analyses were conducted on the Genetic Cluster Computer, which is financially supported by the Netherlands Scientific Organization (NOW; 480-05-003) along with a supplement from the Dutch Brain Foundation and VU University. The Danish iPSYCH (The Lundbeck Foundation Initiative for Integrative Psychiatric Research) and GEMS2 teams acknowledge funding from The Lundbeck Foundation (grant no R102-A9118 and R155-2014-1724), the Stanley Medical Research Institute, an Advanced Grant from the European Research Council (project no: 294838), the Danish Strategic Research Council and grants from Aarhus University to the iSEQ and CIRRAU centers. The Danish National Biobank resource at Statens Serum Institut was supported by the Novo Nordisk Foundation. Computational resources for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility were provided by the iSEQ center, Aarhus University, Denmark (grant to ADB).
- Subjects :
- Multifactorial Inheritance
Schizophrenia/genetics
Genome-wide association study
Disease
Medical and Health Sciences
0302 clinical medicine
Risk Factors
schizophrenia, genetics, risk
2.1 Biological and endogenous factors
genetics
polygenic score
Aetiology
genome wide association study
risk
Genetics
Psychiatry
0303 health sciences
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Genetic Predisposition to Disease/genetics
Single Nucleotide
Genomics
Biological Sciences
Serious Mental Illness
Polymorphism, Single Nucleotide/genetics
Penetrance
3. Good health
Psychiatry and Mental health
Mental Health
Mendelian disease
Erfðarannsóknir
Life Sciences & Biomedicine
Single Nucleotide/genetics
Biochemistry & Molecular Biology
Schizophrenia (object-oriented programming)
high risk
Biology
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Geðklofi
Humans
Genetic Predisposition to Disease
ddc:610
Allele
Polymorphism
Resilience (network)
Molecular Biology
resilience
Multifactorial Inheritance/genetics
Alleles
030304 developmental biology
Science & Technology
Prevention
Human Genome
Psychology and Cognitive Sciences
Neurosciences
Brain Disorders
Lundbeck Foundation Initiative for Integrative Psychiatric Research
schizophrenia
Good Health and Well Being
Schizophrenia
Neurosciences & Neurology
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 14765578 and 13594184
- Volume :
- 26
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecular Psychiatry
- Accession number :
- edsair.doi.dedup.....3471197df8fec836d8bcf93e6e4b37fd