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

Mitja I. Kurki, Elmo Christian Saarentaus, Olli Pietiläinen, Padraigh Gormley, Dennis Lal, Sini Kerminen, Minna Torniainen-Holm, Eija Hämäläinen, Elisa Rahikkala, Riikka Keski-Filppula, Merja Rauhala, Satu Korpi-Heikkila, Jonna Komulainen-Ebrahim, Heli Helander, Päivi Vieira, Minna Männikkö, Markku Peltonen, Aki Havulinna, Veikko Salomaa, Matti PirinenJaana Suvisaari, Jukka S. Moilanen, Jarmo Körkkö, Outi Kuismin, Mark Daly, Aarno Palotie

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Sammanfattning

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.
Originalspråkengelska
Artikelnummer410
TidskriftNature Communications
Volym10
Utgåva1
Antal sidor15
ISSN2041-1723
DOI
StatusPublicerad - 24 jan 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

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  • 1184 Genetik, utvecklingsbiologi, fysiologi
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