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

Author

Listed:
  • Mitja I. Kurki

    (Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston
    The Broad Institute of MIT and Harvard
    University of Helsinki)

  • Elmo Saarentaus

    (University of Helsinki)

  • Olli Pietiläinen

    (The Broad Institute of MIT and Harvard
    University of Harvard, Cambridge)

  • Padhraig Gormley

    (Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston
    The Broad Institute of MIT and Harvard)

  • Dennis Lal

    (Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston
    The Broad Institute of MIT and Harvard)

  • Sini Kerminen

    (University of Helsinki)

  • Minna Torniainen-Holm

    (University of Helsinki
    National Institute for Health and Welfare)

  • Eija Hämäläinen

    (University of Helsinki)

  • Elisa Rahikkala

    (University of Oulu
    University of Oulu
    Oulu University Hospital)

  • Riikka Keski-Filppula

    (University of Oulu
    University of Oulu
    Oulu University Hospital)

  • Merja Rauhala

    (Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care)

  • Satu Korpi-Heikkilä

    (Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care)

  • Jonna Komulainen–Ebrahim

    (Oulu University Hospital, Medical Research Center Oulu, University of Oulu)

  • Heli Helander

    (Oulu University Hospital, Medical Research Center Oulu, University of Oulu)

  • Päivi Vieira

    (Oulu University Hospital, Medical Research Center Oulu, University of Oulu)

  • Minna Männikkö

    (University of Oulu
    University of Oulu)

  • Markku Peltonen

    (National Institute for Health and Welfare)

  • Aki S. Havulinna

    (University of Helsinki
    National Institute for Health and Welfare)

  • Veikko Salomaa

    (National Institute for Health and Welfare)

  • Matti Pirinen

    (University of Helsinki)

  • Jaana Suvisaari

    (National Institute for Health and Welfare)

  • Jukka S. Moilanen

    (University of Oulu
    University of Oulu
    Oulu University Hospital)

  • Jarmo Körkkö

    (Northern Ostrobothnia Hospital District, Center for Intellectual Disability Care)

  • Outi Kuismin

    (University of Helsinki
    University of Oulu
    University of Oulu
    Oulu University Hospital)

  • Mark J. Daly

    (Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston
    The Broad Institute of MIT and Harvard
    University of Helsinki
    Massachusetts General Hospital)

  • Aarno Palotie

    (Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston
    The Broad Institute of MIT and Harvard
    University of Helsinki
    Massachusetts General Hospital)

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.

Suggested Citation

  • Mitja I. Kurki & Elmo Saarentaus & Olli Pietiläinen & Padhraig Gormley & Dennis Lal & Sini Kerminen & Minna Torniainen-Holm & Eija Hämäläinen & Elisa Rahikkala & Riikka Keski-Filppula & Merja Rauhala , 2019. "Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08262-y
    DOI: 10.1038/s41467-018-08262-y
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