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Nat Commun DOI:10.1038/s41467-018-08262-y

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

Publication TypeJournal Article
Year of Publication2019
AuthorsKurki, MI, Saarentaus, E, Pietilainen, O, Gormley, P, Lal, D, Kerminen, S, Torniainen-Holm, M, Hämäläinen, E, Rahikkala, E, Keski-Filppula, R, Rauhala, M, Korpi-Heikkilä, S, Komulainen-Ebrahim, J, Helander, H, Vieira, P, Männikkö, M, Peltonen, M, Havulinna, AS, Salomaa, V, Pirinen, M, Suvisaari, J, Moilanen, JS, Körkkö, J, Kuismin, O, Daly, MJ, Palotie, A
JournalNat Commun
Date Published2019 01 24
KeywordsCognitive Dysfunction, Cohort Studies, CRADD Signaling Adaptor Protein, DNA Copy Number Variations, Exome, Female, Finland, Genetic Association Studies, Genetic Diseases, Inborn, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Geography, Homozygote, Humans, Intellectual Disability, Male, Multifactorial Inheritance, Mutation, Neurodevelopmental Disorders, Pathology, Molecular, Prevalence, Whole Exome Sequencing

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.


Alternate JournalNat Commun
PubMed ID30679432
PubMed Central IDPMC6345990