Imaging genetics of language network functional connectivity reveals links with language-related abilities, dyslexia and handedness

• Published in: Communications biology Vol. 7; no. 1; pp. 1209 - 13
• Main Authors: Amelink, Jitse S., Postema, Merel C., Kong, Xiang-Zhen, Schijven, Dick, Carrión-Castillo, Amaia, Soheili-Nezhad, Sourena, Sha, Zhiqiang, Molz, Barbara, Joliot, Marc, Fisher, Simon E., Francks, Clyde
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/205/2138; 631/378/2583; Adult; Aged; Association analysis; Asymmetry; Biomedical and Life Sciences; Brain - diagnostic imaging; Brain - physiology; Brain architecture; Brain Mapping - methods; Cerebral hemispheres; Dyslexia; Dyslexia - genetics; Dyslexia - physiopathology; Female; Functional Laterality - genetics; Functional morphology; Gene frequency; Genetic analysis; Genetic diversity; Genome-Wide Association Study; Genomic analysis; Handedness; Hemispheric laterality; Humans; Language; Life Sciences; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net - physiology; Neural networks; Neuroimaging; Polygenic inheritance; Population genetics
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06890-3

Language is supported by a distributed network of brain regions with a particular contribution from the left hemisphere. A multi-level understanding of this network requires studying its genetic architecture. We used resting-state imaging data from 29,681 participants (UK Biobank) to measure connectivity between 18 left-hemisphere regions involved in multimodal sentence-level processing, as well as their right-hemisphere homotopes, and interhemispheric connections. Multivariate genome-wide association analysis of this total network, based on genetic variants with population frequencies  >1%, identified 14 genomic loci, of which three were also associated with asymmetry of intrahemispheric connectivity. Polygenic dispositions to lower language-related abilities, dyslexia and left-handedness were associated with generally reduced leftward asymmetry of functional connectivity. Exome-wide association analysis based on rare, protein-altering variants (frequencies <1%) suggested 7 additional genes. These findings shed new light on genetic contributions to language network organization and related behavioural traits. Common and rare genetic variants, as well as polygenic scores of dyslexia and handedness are associated with the functional brain language network and hemispheric differences within this network, shedding light on its developmental basis.