Biology subjects

Naerland, T.

Publications and source records attributed to Naerland, T..

3 recordsLinked to original sources

bioRxiv2022

Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion MRI). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N=34,029) and ABCD Study (N=8,607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individually. Cross-modality genes are involved in fundamental biological processes and predominantly expressed during prenatal brain development. We additionally boost prediction of psychiatric disorders by conditioning independent GWAS on our multimodal multivariate GWAS. These findings shed light on the shared genetic mechanisms underlying variation in brain morphology, functional connectivity, and tissue composition. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/521181v3_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@1e7eadcorg.highwire.dtl.DTLVardef@ec127eorg.highwire.dtl.DTLVardef@b21f14org.highwire.dtl.DTLVardef@1690c5_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2018

Sex differences in the relationship between social difficulties and executive dysfunction in children and adolescents with autism spectrum disorder

The prevalence of autism spectrum disorder (ASD) in boys is nearly four times higher than in girls, and the causes of this sex difference are not fully known. Difficulties in executive function may be involved in development of autistic symptomatology. Here we investigated sex differences in the relationship between executive function in everyday life and social dysfunction symptoms in a sample of 116 children (25 girls) aged 5-19 years with IQ above 70 and with a diagnosis of ASD. They were assessed with the Behavior Rating Inventory of Executive Function (BRIEF) and the Autism Diagnostic Interview Revised (ADI-R). We found no significant differences in BRIEF or ADI-R scores between girls and boys after correcting for multiple testing. Nested linear regression models revealed significant sex differences in the relationship between executive function and both reciprocal social interaction (p<0.001) and communication (p=0.001) over and above the main effects of age, sex, IQ and comorbid attention deficit/hyperactivity disorder diagnosis. We did not find sex differences in the relationship between executive dysfunction and restricted and repetitive behaviors. Altogether, our results provide a greater understanding of the sex-specific characteristics of ASD and may suggest that boys and girls can benefit from different intervention strategies.

neuroscience↗

bioRxiv2017

Common risk variants identified in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes, in contrast to what is typically seen in other complex disorders. These results highlight biological insights, particularly relating to neuronal function and corticogenesis and establish that GWAS performed at scale will be much more productive in the near term in ASD, just as it has been in a broad range of important psychiatric and diverse medical phenotypes.

genetics↗