Bidirectional genetic overlap between autism spectrum disorder and cognitive traits

Autism spectrum disorder (ASD) is a highly heritable condition with a large variation in cognitive function. Here we investigated the shared genetic architecture between cognitive traits (intelligence (INT) and educational attainment (EDU)), and risk loci jointly associated with ASD and the cognitiv...

Full description

Saved in:
Bibliographic Details
Published in:Translational psychiatry 2023-09, Vol.13 (1), p.295-9, Article 295
Main Authors: Hope, Sigrun, Shadrin, Alexey A., Lin, Aihua, Bahrami, Shahram, Rødevand, Linn, Frei, Oleksandr, Hübenette, Saira J., Cheng, Weiqiu, Hindley, Guy, Nag, Heidi, Ulstein, Line, Efrim-Budisteanu, Magdalena, O’Connell, Kevin, Dale, Anders M., Djurovic, Srdjan, Nærland, Terje, Andreassen, Ole A.
Format: Article
Language:English
Subjects:
45
45/43
631/208
692/420/2489
692/699/476/1373
Autism
Behavioral Sciences
Biological Psychology
Gene loci
Medicine
Medicine & Public Health
Neurosciences
Pharmacotherapy
Psychiatry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Autism spectrum disorder (ASD) is a highly heritable condition with a large variation in cognitive function. Here we investigated the shared genetic architecture between cognitive traits (intelligence (INT) and educational attainment (EDU)), and risk loci jointly associated with ASD and the cognitive traits. We analyzed data from genome-wide association studies (GWAS) of INT ( n  = 269,867), EDU ( n  = 766,345) and ASD (cases n  = 18,381, controls n  = 27,969). We used the bivariate causal mixture model (MiXeR) to estimate the total number of shared genetic variants, local analysis of co-variant annotation (LAVA) to estimate local genetic correlations, conditional false discovery rate (cond/conjFDR) to identify specific overlapping loci. The MiXeR analyses showed that 12.7k genetic variants are associated with ASD, of which 12.0k variants are shared with EDU, and 11.1k are shared with INT with both positive and negative relationships within overlapping variants. The majority (59–68%) of estimated shared loci have concordant effect directions, with a positive, albeit modest, genetic correlation between ASD and EDU (r g  = 0.21, p  = 2e−13) and INT (r g  = 0.22, p  = 4e−12). We discovered 43 loci jointly associated with ASD and cognitive traits (conjFDR
ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-023-02563-7