Journal Article

FZJ-2020-02533

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Quantitative genome-wide association study of six phenotypic subdomains identifies novel genome-wide significant variants in autism spectrum disorder.

Yousaf, A. (Corresponding author) ; Waltes, R. ; Haslinger, D. ; Klauck, S. M. ; Duketis, E. ; Sachse, M. ; Voran, A. ; Biscaldi, M. ; Schulte-Rüther, M. (Corresponding author)FZJ* ; Cichon, S.FZJ* ; Nöthen, M. ; Ackermann, J. ; Koch, I. ; Freitag, C. M. ; Chiocchetti, A. G.

2020
Nature Publishing Group London

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/25273  doi:10.1038/s41398-020-00906-2

Abstract: Autism spectrum disorders (ASD) are highly heritable and are characterized by deficits in social communication and restricted and repetitive behaviors. Twin studies on phenotypic subdomains suggest a differing underlying genetic etiology. Studying genetic variation explaining phenotypic variance will help to identify specific underlying pathomechanisms. We investigated the effect of common variation on ASD subdomains in two cohorts including >2500 individuals. Based on the Autism Diagnostic Interview-Revised (ADI-R), we identified and confirmed six subdomains with a SNP-based genetic heritability h2SNP = 0.2-0.4. The subdomains nonverbal communication (NVC), social interaction (SI), and peer interaction (PI) shared genetic risk factors, while the subdomains of repetitive sensory-motor behavior (RB) and restricted interests (RI) were genetically independent of each other. The polygenic risk score (PRS) for ASD as categorical diagnosis explained 2.3-3.3% of the variance of SI, joint attention (JA), and PI, 4.5% for RI, 1.2% of RB, but only 0.7% of NVC. We report eight genome-wide significant hits-partially replicating previous findings-and 292 known and novel candidate genes. The underlying biological mechanisms were related to neuronal transmission and development. At the SNP and gene level, all subdomains showed overlap, with the exception of RB. However, no overlap was observed at the functional level. In summary, the ADI-R algorithm-derived subdomains related to social communication show a shared genetic etiology in contrast to restricted and repetitive behaviors. The ASD-specific PRS overlapped only partially, suggesting an additional role of specific common variation in shaping the phenotypic expression of ASD subdomains.

---

Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)
2. Jara-Institut Quantum Information (INM-11)

Research Program(s):

1. 571 - Connectivity and Activity (POF3-571) (POF3-571)
2. HBP SGA3 - Human Brain Project Specific Grant Agreement 3 (945539) (945539)
3. HBP SGA2 - Human Brain Project Specific Grant Agreement 2 (785907) (785907)

Appears in the scientific report 2020

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---