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

Autor: Kurki MI; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland., Saarentaus E; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland., Pietiläinen O; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Department of Stem Cell and Regenerative Biology, University of Harvard, Cambridge, MA, 02138, USA., Gormley P; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA., Lal D; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA., Kerminen S; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland., Torniainen-Holm M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland.; National Institute for Health and Welfare, 00271, Helsinki, Finland., Hämäläinen E; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland., Rahikkala E; PEDEGO Research Unit, University of Oulu, FI-90014, Oulu, Finland.; Medical Research Center, Oulu University Hospital,, University of Oulu, FI-90014, Oulu, Finland.; Department of Clinical Genetics, Oulu University Hospital, 90220, Oulu, Finland., Keski-Filppula R; PEDEGO Research Unit, University of Oulu, FI-90014, Oulu, Finland.; Medical Research Center, Oulu University Hospital,, University of Oulu, FI-90014, Oulu, Finland.; Department of Clinical Genetics, Oulu University Hospital, 90220, Oulu, Finland., Rauhala M; Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care, 90220, Oulu, Finland., Korpi-Heikkilä S; Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care, 90220, Oulu, Finland., Komulainen-Ebrahim J; Department of Children and Adolescents, Oulu University Hospital, Medical Research Center Oulu, University of Oulu, FI-90029, Oulu, Finland., Helander H; Department of Children and Adolescents, Oulu University Hospital, Medical Research Center Oulu, University of Oulu, FI-90029, Oulu, Finland., Vieira P; Department of Children and Adolescents, Oulu University Hospital, Medical Research Center Oulu, University of Oulu, FI-90029, Oulu, Finland., Männikkö M; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Infrastructure for population studies, Faculty of Medicine, University of Oulu, Oulu, Finland., Peltonen M; National Institute for Health and Welfare, 00271, Helsinki, Finland., Havulinna AS; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland.; National Institute for Health and Welfare, 00271, Helsinki, Finland., Salomaa V; National Institute for Health and Welfare, 00271, Helsinki, Finland., Pirinen M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland., Suvisaari J; National Institute for Health and Welfare, 00271, Helsinki, Finland., Moilanen JS; PEDEGO Research Unit, University of Oulu, FI-90014, Oulu, Finland.; Medical Research Center, Oulu University Hospital,, University of Oulu, FI-90014, Oulu, Finland.; Department of Clinical Genetics, Oulu University Hospital, 90220, Oulu, Finland., Körkkö J; Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care, 90220, Oulu, Finland., Kuismin O; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland.; PEDEGO Research Unit, University of Oulu, FI-90014, Oulu, Finland.; Medical Research Center, Oulu University Hospital,, University of Oulu, FI-90014, Oulu, Finland.; Department of Clinical Genetics, Oulu University Hospital, 90220, Oulu, Finland., Daly MJ; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland.; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.; Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA., Palotie A; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA. aarno.palotie@helsinki.fi.; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. aarno.palotie@helsinki.fi.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Helsinki, Finland. aarno.palotie@helsinki.fi.; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. aarno.palotie@helsinki.fi.; Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA. aarno.palotie@helsinki.fi.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Jan 24; Vol. 10 (1), pp. 410. Date of Electronic Publication: 2019 Jan 24.
DOI: 10.1038/s41467-018-08262-y
Abstrakt: 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.
Databáze: MEDLINE