The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses

Abstract

Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with handedness and language lateralization. Significant gene ontology sets for handedness were anatomical structure development, pattern specification (especially asymmetry formation) and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that handedness and language lateralization are ontogenetically independent, complex phenotypes.

Mood episodes are associated with increased cortical thinning: A longitudinal study of bipolar disorder type II

“…38 Interestingly, some previous studies found an association between depressive episodes and GM loss and cortical thinning in left inferior temporal regions overlapping with the regions found in this study. 39 Importantly, however, uncorrected results of our analyses also indicated an association between depressive episodes and right temporal cortical thinning (Figure 2A,E) and the laterality of our results should therefore be interpreted with caution. 5 Although the mechanisms underlying the potential lateralization effects of BD remain unknown, genes involved in handedness and language lateralization were associated with depression and BD in a recent study.…”

“…5 Although the mechanisms underlying the potential lateralization effects of BD remain unknown, genes involved in handedness and language lateralization were associated with depression and BD in a recent study. 39 Importantly, however, uncorrected results of our analyses also indicated an association between depressive episodes and right temporal cortical thinning (Figure 2A,E) and the laterality of our results should therefore be interpreted with caution.…”

Right‐handed fossil humans

“…The same is true for a direct connection between handedness and language areas of the brain. 93 The two traits appear to be determined by different gene complexes. [88][89][90][91] In living humans, gestural and spoken language is primarily a left hemisphere function; the same hemisphere directs the right hand.…”

“…93 As Fitch and Braccini 98 maintain, "[h]uman handedness, rather than being a driving force, may be a by-product of more fundamental perceptual and cognitive asymmetries, particularly those involved in language evolution." 93 As Fitch and Braccini 98 maintain, "[h]uman handedness, rather than being a driving force, may be a by-product of more fundamental perceptual and cognitive asymmetries, particularly those involved in language evolution."…”

The Chain of Chirality Transfer as Determinant of Brain Functional Laterality. Breaking the Chirality Silence: Search for New Generation of Biomarkers; Relevance to Neurodegenerative Diseases, Cognitive Psychology, and Nutrition Science

“…Even the reviews devoted to structure, function, and assembly of the visual system (which is lateralized and well-studied as one of the most asymmetrical) do not focused on the molecular substrate of sensory functions. The explosive attention to protein-brain topology demonstrated in this year's publications can be considered as a response to the "necessity calls'' [250,245,251,252].…”