Imaging-genetics of sex differences in ASD: distinct effects of OXTR variants on brain connectivity.

Translational Psychiatry
L M HernandezGENDAAR Consortium

Abstract

Autism spectrum disorder (ASD) is more prevalent in males than in females, but the neurobiological mechanisms that give rise to this sex-bias are poorly understood. The female protective hypothesis suggests that the manifestation of ASD in females requires higher cumulative genetic and environmental risk relative to males. Here, we test this hypothesis by assessing the additive impact of several ASD-associated OXTR variants on reward network resting-state functional connectivity in males and females with and without ASD, and explore how genotype, sex, and diagnosis relate to heterogeneity in neuroendophenotypes. Females with ASD who carried a greater number of ASD-associated risk alleles in the OXTR gene showed greater functional connectivity between the nucleus accumbens (NAcc; hub of the reward network) and subcortical brain areas important for motor learning. Relative to males with ASD, females with ASD and higher OXTR risk-allele-dosage showed increased connectivity between the NAcc, subcortical regions, and prefrontal brain areas involved in mentalizing. This increased connectivity between NAcc and prefrontal cortex mirrored the relationship between genetic risk and brain connectivity observed in neurotypical males showing...Continue Reading

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Citations

Jun 4, 2020·Translational Psychiatry·Katherine E LawrenceUNKNOWN GENDAAR Consortium
Mar 3, 2021·Molecular Autism·Dorothea L FlorisAdriana Di Martino
Dec 2, 2020·Current Opinion in Neurobiology·Charles L Ford, Larry J Young

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Methods Mentioned

BETA
Genotyping

Software Mentioned

FSL Motion Correction Linear Registration Tool ( MCFLIRT )
GENDAAR
FSL
FSL Automatic Segmentation Tool ( FAST )
Power
FLAME
PLINK
FEAT
FSL FEAT
AFNI ( Analysis of Functional NeuroImages )

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