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How "dyslexia genes" influence brain structure and connectivity?

Presented During:

Language: Anatomy, Networks and Pathology

Thursday, June 26, 2025: 11:30 AM - 12:45 PM

Brisbane Convention & Exhibition Centre

Room: M4 (Mezzanine Level)

Poster No:

685

Submission Type:

Abstract Submission

Authors:

Jingjing Zhao¹, Yueye Zhao², Hayley Mountford³, Colin Buchanan³, Joanna Moodie³, Heather Whalley⁴, Simon Cox³, Michelle Luciano³

Institutions:

¹Department of Psychology, The Chinese University of Hong Kong, Shatin, Hong Kong, ²School of Psychology, Shaanxi Normal University, Xi'an, China, ³Department of Psychology, University of Edinburgh, Edinburgh, UK, ⁴Department of Psychiatry, University of Edinburgh, Edinburgh, UK

First Author:

Jingjing Zhao
Department of Psychology, The Chinese University of Hong Kong
Shatin, Hong Kong

Co-Author(s):

Yueye Zhao
School of Psychology, Shaanxi Normal University
Xi'an, China

Hayley Mountford
Department of Psychology, University of Edinburgh
Edinburgh, UK

Colin Buchanan
Department of Psychology, University of Edinburgh
Edinburgh, UK

Joanna Moodie
Department of Psychology, University of Edinburgh
Edinburgh, UK

Heather Whalley
Department of Psychiatry, University of Edinburgh
Edinburgh, UK

Simon Cox
Department of Psychology, University of Edinburgh
Edinburgh, UK

Michelle Luciano
Department of Psychology, University of Edinburgh
Edinburgh, UK

Introduction:

Dyslexia is a common learning disability affecting the acquisition of fluent reading skills. It is a heritable neurodevelopmental disorder that is known as a neural disconnection syndrome. Yet, how dyslexia related genes influence brain structure and connectivity has been rarely explored. In this study, we investigated whether and how human brain structure and connectivity are influenced by genetic underpinnings of dyslexia.

Methods:

UK Biobank dataset with structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) data from 40,360 adults between 44- and 83-year-olds was used as a discovery sample. We focused on grey matter volumes of 85 brain regions (17 subcortical and 68 cortical regions), surface area and cortical thickness of 68 cortical regions, as well as white matter connectivity estimated using standard DTI model (e.g., fractional anisotropy (FA) and streamline count (SC)) and advanced NODDI (neurite orientation dispersion and density imaging) model (e.g., orientation dispersion (OD)) for the 85 brain regions derived from whole brain connectome analysis. Polygenic scores of dyslexic susceptibilities, reading and spelling abilities, and phonological processing abilities were computed for these participants. General linear models were employed for correlations between polygenic scores and grey matter volume, surface area and cortical thickness. Cross-dataset validation on gray matter structure was conducted using an independent sample from the Generation Scotland: Scottish Family Health Study dataset with 938 adults between 18- and 75-year-olds. Validated correlations were further verified by cross-modal white matter connectivity measures.

·Figure 1. The flowchart for the primary analysis and validation stages.

Results:

The discovery sample of UK Biobank revealed associations between polygenic scores of dyslexia and grey matter volume, surface area and cortical thickness of a number of phonological and reading-related regions, including the left insula, fusiform gyrus, superior temporal gyrus, inferior parietal gyrus, and parsorbitalis frontal gyrus. In particular, results in grey matter volume and surface area of the left insula were replicated by the independent sample of Generation Scotland as well as by various white matter connectivity measures including FA, SC, and OD in UK Biobank. Further mediation analysis with UK Biobank dataset showed that polygenic scores of dyslexia influenced phonological memory (measured by digit span) through grey matter volume of the left insula.

·Figure 2. The binned scatter plots of the main results

Conclusions:

Our results highlight the influence of "dyslexia genes" on brain structure and connectivity of the left insula. The current findings might support the phonological deficit theory of dyslexia, particularly in phonological memory deficit. Given the important role of insula in interoceptive awareness and appraisal of one's own internal states, as well as in speech articulation, the discovery of insula might alternatively support motor-articulatory feedback hypothesis of dyslexia, i.e. dyslexic children suffer from an inability to associate the position of their articulators with speech sounds.

Disorders of the Nervous System:

Neurodevelopmental/ Early Life (eg. ADHD, autism)

Genetics:

Genetic Association Studies ¹

Language:

Reading and Writing

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Anatomy and Brain Mapping ²

Novel Imaging Acquisition Methods:

Diffusion MRI

Keywords:

Computational Neuroscience

Cortex

DISORDERS

Language

MRI

STRUCTURAL MRI

Structures

White Matter

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC

Other - Dyslexia;Gene; Polygenic scores; Insula

^1|2Indicates the priority used for review

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Smith Stephen M A-aF, Miller Karla L. UK Biobank Brain Imaging Documentation. 2020 (Version 1.8).

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