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

Nat Commun
Authors
Keywords
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.

Year of Publication
2019
Journal
Nat Commun
Volume
10
Issue
1
Pages
410
Date Published
2019 01 24
ISSN
2041-1723
DOI
10.1038/s41467-018-08262-y
PubMed ID
30679432
PubMed Central ID
PMC6345990
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