A family-based study of genetic and epigenetic effects across multiple neurocognitive, motor, social-cognitive and social-behavioral functions.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_2831051D9816
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A family-based study of genetic and epigenetic effects across multiple neurocognitive, motor, social-cognitive and social-behavioral functions.
Journal
Behavioral and brain functions
Author(s)
Nudel R., Zetterberg R., Hemager N., Christiani CAJ, Ohland J., Burton B.K., Greve A.N., Spang K.S., Ellersgaard D., Gantriis D.L., Bybjerg-Grauholm J., Plessen K.J., Jepsen JRM, Thorup AAE, Werge T., Mors O., Nordentoft M.
ISSN
1744-9081 (Electronic)
ISSN-L
1744-9081
Publication state
Published
Issued date
01/12/2022
Peer-reviewed
Oui
Volume
18
Number
1
Pages
14
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case-control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene → endophenotype → disorder pathways.
Keywords
Genes, Regulator, Epigenomics, Endophenotypes, Cognition, Epigenesis, Genetic, Cognitive functions, Endophenotype, GWAS, Neurodevelopment, Parent-of-origin effect
Pubmed
Web of science
Open Access
Yes
Create date
12/12/2022 11:49
Last modification date
23/01/2024 7:22
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