Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children

Skeide, Michael; Kirsten, Holger; Kraft, Indra; Schaadt, Gesa; Müller, Bent; Neef, Nicole E.; Bräuer, Jens; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes; Friederici, Angela D.

doi:10.1016/j.neuroimage.2015.06.024

Cited by 41 publications

(27 citation statements)

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“…Importantly, the study by Skeide et al. (2015) and the present analysis were conducted in overlapping cohorts, which further strengthen the proposed connection between the functional connectivity of the fronto‐temporal processing hubs, altered late component of the MMR and rs11100040.…”

Section: Discussionsupporting

confidence: 83%

“…Here, we could also identify a nominal significant association of rs11100040 with the late component of the MMR. Interestingly, in a recent study, we were able to show that rs11100040 also affects the functional connectivity of the fronto‐temporal processing hubs in German native speakers (Skeide et al., 2015). The reduced functional connectivity between frontal and temporal brain areas might provide the basis for the dyslexia‐related modulation of the late component of the MMR because at least two regions are involved in generating the MMR: a frontal source is located in the inferior frontal gyrus and a temporal source located in the superior temporal gyrus (Doeller et al., 2003; Marco‐Pallarés, Grau, & Ruffini, 2005).…”

Section: Discussionmentioning

confidence: 99%

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ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

et al. 2017

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BackgroundDyslexia is a specific learning disorder affecting reading and spelling abilities. Its prevalence is ~5% in German‐speaking individuals. Although the etiology of dyslexia largely remains to be determined, comprehensive evidence supports deficient phonological processing as a major contributing factor. An important prerequisite for phonological processing is auditory discrimination and, thus, essential for acquiring reading and spelling skills. The event‐related potential Mismatch Response (MMR) is an indicator for auditory discrimination capabilities with dyslexics showing an altered late component of MMR in response to auditory input.MethodsIn this study, we comprehensively analyzed associations of dyslexia‐specific late MMRs with genetic variants previously reported to be associated with dyslexia‐related phenotypes in multiple studies comprising 25 independent single‐nucleotide polymorphisms (SNPs) within 10 genes.ResultsFirst, we demonstrated validity of these SNPs for dyslexia in our sample by showing that additional inclusion of a polygenic risk score improved prediction of impaired writing compared with a model that used MMR alone. Secondly, a multifactorial regression analysis was conducted to uncover the subset of the 25 SNPs that is associated with the dyslexia‐specific late component of MMR. In total, four independent SNPs within DYX1C1 and ATP2C2 were found to be associated with MMR stronger than expected from multiple testing. To explore potential pathomechanisms, we annotated these variants with functional data including tissue‐specific expression analysis and eQTLs.ConclusionOur findings corroborate the late component of MMR as a potential endophenotype for dyslexia and support tripartite relationships between dyslexia‐related SNPs, the late component of MMR and dyslexia.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

et al. 2017

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“…Indeed, Skeide and colleagues reported an example of such a genetic risk variant for dyslexia. They showed that this variant is related to the functional connectivity of left fronto-temporal phonological processing areas during the resting state 52 . Similarly, children with higher arithmetic scores present a more mature response modulation in their left intraparietal lobe 47 .…”

Section: Discussionmentioning

confidence: 99%

Shared genetic aetiology between cognitive performance and brain activations in language and math tasks

Guen

Amalric

Pinel

et al. 2018

Preprint

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Corresponding authors' information:Emails: yann.leguen@cea.fr (YLG), vincent.frouin@cea.fr (VF) 2 Cognitive performance is highly heritable. However, little is known about common genetic influences on cognitive ability and brain activation when engaged in a cognitive task. The Human Connectome Project (HCP) offers a unique opportunity to study this shared genetic etiology with an extended pedigree of 785 individuals. To investigate this common genetic origin, we took advantage of the HCP dataset, which includes both language and mathematics activation tasks. Using the HCP multimodal parcellation, we identified areals in which interindividual functional MRI (fMRI) activation variance was significantly explained by genetics.Then, we performed bivariate genetic analyses between the neural activations and behavioral scores, corresponding to the fMRI task accuracies, fluid intelligence, working memory and language performance. We observed that several parts of the language network along the superior temporal sulcus, as well as the angular gyrus belonging to the math processing network, are significantly genetically correlated with these indicators of cognitive performance. This shared genetic etiology provides insights into the brain areas where the human-specific genetic repertoire is expressed. Studying the association of polygenic risk scores, using variants associated with human cognitive ability and brain activation, would provide an opportunity to better understand where these variants are influential.

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“…Both SNPs were associated with regulation of the glucose transport gene SLC2A3 , leading the authors to propose that the attenuated MMN response observed in children with SRD may arise from reduced glucose resulting from the modulation of SLC2A3 expression by rs4234898 and rs11100040. In another investigation, Skeide et al () reported reduced functional and structural connectivity among left hemisphere reading/language regions in children carrying the risk‐allele at rs11100040. Additional research will be needed to investigate a potential causal mechanism among these SNPs, regulation of SLC2A3 , connectivity, and reading and language abilities.…”

Section: Additional Genes Linked To Reading and Languagementioning

confidence: 95%

Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review

Landi

Perdue

2019

Language and Linguist. Compass

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Developmental disorders of spoken and written language are heterogeneous in nature with impairments observed across various linguistic, cognitive, and sensorimotor domains. These disorders are also associated with characteristic patterns of atypical neural structure and function that are observable early in development, often before formal schooling begins. Established patterns of heritability point toward genetic contributions, and molecular genetics approaches have identified genes that play a role in these disorders. Still, identified genes account for only a limited portion of phenotypic variance in complex developmental disorders, described as the problem of “missing heritability.” The characterization of intermediate phenotypes at the neural level may fill gaps in our understanding of heritability patterns in complex disorders, and the emerging field of neuroimaging genetics offers a promising approach to accomplish this goal. The neuroimaging genetics approach is gaining prevalence in language- and reading-related research as it is well-suited to incorporate behavior, genetics, and neurobiology into coherent etiological models of complex developmental disorders. Here, we review research applying the neuroimaging genetics approach to the study of specific reading disability (SRD) and developmental language disorder (DLD), much of which links genes with known neurodevelopmental function to functional and structural abnormalities in the brain.

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Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children

Cited by 41 publications

References 54 publications

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

Shared genetic aetiology between cognitive performance and brain activations in language and math tasks

Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review

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