University of Oulu
Oulu University Library
OuluCRIS
Laturi
Muuntaja

Similar Items

Cover Image

Kurki, M.I., Saarentaus, E., Pietiläinen, O. et al. Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland. Nat Commun 10, 410 (2019). https://doi.org/10.1038/s41467-018-08262-y

Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland

Saved in:
Author: Kurki, Mitja I.1,2,3; Saarentaus, Elmo3; Pietiläinen, Olli2,4;
Organizations: 1Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA
2The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
3Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland
4Department of Stem Cell and Regenerative Biology, University of Harvard, Cambridge, MA, 02138, USA
5National Institute for Health and Welfare, 00271, Helsinki, Finland
6PEDEGO Research Unit, University of Oulu, FI-90014, Oulu, Finland
7Medical Research Center, Oulu University Hospital,, University of Oulu, FI-90014, Oulu, Finland
8Department of Clinical Genetics, Oulu University Hospital, 90220, Oulu, Finland
9Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care, 90220, Oulu, Finland
10Department of Children and Adolescents, Oulu University Hospital, Medical Research Center Oulu, University of Oulu, FI-90029, Oulu, Finland
11Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
12Infrastructure for population studies, Faculty of Medicine, University of Oulu, Oulu, Finland
13Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
14Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202003309589
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-03-30
Description:

Abstract

The contribution of de novo variants in severe intellectual disability (ID) has been extensively studied whereas the genetics of mild ID has been less characterized. To elucidate the genetics of milder ID we studied 442 ID patients enriched for mild ID (>50%) from a population isolate of Finland. Using exome sequencing, we show that rare damaging variants in known ID genes are observed significantly more often in severe (27%) than in mild ID (13%) patients. We further observe a significant enrichment of functional variants in genes not yet associated with ID (OR: 2.1). We show that a common variant polygenic risk significantly contributes to ID. The heritability explained by polygenic risk score is the highest for educational attainment (EDU) in mild ID (2.2%) but lower for more severe ID (0.6%). Finally, we identify a Finland enriched homozygote variant in the CRADD ID associated gene.

see all
Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 10
Article number: 410
DOI: 10.1038/s41467-018-08262-y
OADOI: https://oadoi.org/10.1038/s41467-018-08262-y
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Article
Funding: We thank Social Science Genetic Association Consortium (SSGAC; www.thessgac.org), Psychiatric Genomics Consortium (PGC;Stephan Ripke; http://www.med.unc.edu/pgc), and Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (http://ctg.cncr.nl/) for sharing summary statistics of their GWAS studies. We further thank SSGAC and PGC for kindly re-generating variant weights excluding Finnish cohorts. O.P. was supported by Sigrid Juselius Foundation, Orion Research Foundation, Maud Kuistila Memorial Foundation, Brain Foundation, and Jenny ja Antti Wihuri Foundation. We also acknowledge EU/Horizon2020, COSYN, grant number 667301.
Copyright information: © The Authors 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  https://creativecommons.org/licenses/by/4.0/