Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland
Kurki, Mitja I.; Saarentaus, Elmo; Pietiläinen, Olli; Gormley, Padhraig; Lal, Dennis; Kerminen, Sini; Torniainen-Holm, Minna; Hämäläinen, Eija; Rahikkala, Elisa; Keski-Filppula, Riikka; Rauhala, Merja; Korpi-Heikkilä, Satu; Komulainen–Ebrahim, Jonna; Helander, Heli; Vieira, Päivi; Männikkö, Minna; Peltonen, Markku; Havulinna, Aki S.; Salomaa, Veikko; Pirinen, Matti; Suvisaari, Jaana; Moilanen, Jukka S.; Körkkö, Jarmo; Kuismin, Outi; Daly, Mark J.; Palotie, Aarno (2019-01-24)
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
© 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/
https://urn.fi/URN:NBN:fi-fe202003309589
Tiivistelmä
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.
Kokoelmat
- Avoin saatavuus [31657]