Title Mapping the brain signature of dyslexia risk onto histamine, acetylcholine and glutamate receptor systems
- 1Department of Physiology, Brain and Cognition Research Center (BEYKOG), Istanbul Medipol University, Istanbul, Turkiye; Besikcizade Center for Medical Humanitie
Abstract
The brain differences of dyslexia are well described and its genetic risk is now measurable; the brain systems that connect the two are unknown. That link decides which measures complement one another in early identification and which systems intervention research should examine. Here we compared large-scale polygenic score maps of brain structure in dyslexia with normative maps of brain neurotransmitter systems. The structural signature of genetic liability aligned with the cortical distribution of neurotransmitter systems. The strongest and most consistent alignment appeared for the histamine H3 receptor, the vesicular acetylcholine transporter (VAChT) and the N-methyl-D-aspartate (NMDA) glutamate receptor. The alignment was most pronounced in cingulate, medial and superior frontal cortex and the paracentral lobule. The H3 alignment held after adjustment for cortical position and for metabolic and cognitive reference maps. Once the component common to all nineteen maps and position were removed together, no individual system remained significant, while the shared component itself aligned with liability. The signature therefore follows the topography these systems share. In 169 children, per-person alignment with the H3 map related to reading skill with the opposite sign to liability. To our knowledge, this is the first study to relate the structural signature of genetic liability for dyslexia to normative maps of neurotransmitter receptor and transporter density. It places that signature within the shared geography of the systems that set attention, arousal and synaptic plasticity during learning, and gives the genetics of dyslexia a testable biological axis.
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BibTeX
@misc{celik2026title,
title = {{Title Mapping the brain signature of dyslexia risk onto histamine, acetylcholine and glutamate receptor systems}},
author = {M. C. Celik and Y. Cicek and M. A. Sakiroglu and D. Aslan and A. T. Altunc and H. A. Velioglu},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.18.26365830},
url = {https://www.medrxiv.org/content/10.64898/2026.10.18.26365830v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Title Mapping the brain signature of dyslexia risk onto histamine, acetylcholine and glutamate receptor systems
AU - M. C. Celik
AU - Y. Cicek
AU - M. A. Sakiroglu
AU - D. Aslan
AU - A. T. Altunc
AU - H. A. Velioglu
PY - 2026
DA - 2026/10/18
PB - medRxiv
DO - 10.64898/2026.10.18.26365830
UR - https://www.medrxiv.org/content/10.64898/2026.10.18.26365830v1
AB - The brain differences of dyslexia are well described and its genetic risk is now measurable; the brain systems that connect the two are unknown. That link decides which measures complement one another in early identification and which systems intervention research should examine. Here we compared large-scale polygenic score maps of brain structure in dyslexia with normative maps of brain neurotransmitter systems. The structural signature of genetic liability aligned with the cortical distribution of neurotransmitter systems. The strongest and most consistent alignment appeared for the histamine H3 receptor, the vesicular acetylcholine transporter (VAChT) and the N-methyl-D-aspartate (NMDA) glutamate receptor. The alignment was most pronounced in cingulate, medial and superior frontal cortex and the paracentral lobule. The H3 alignment held after adjustment for cortical position and for metabolic and cognitive reference maps. Once the component common to all nineteen maps and position were removed together, no individual system remained significant, while the shared component itself aligned with liability. The signature therefore follows the topography these systems share. In 169 children, per-person alignment with the H3 map related to reading skill with the opposite sign to liability. To our knowledge, this is the first study to relate the structural signature of genetic liability for dyslexia to normative maps of neurotransmitter receptor and transporter density. It places that signature within the shared geography of the systems that set attention, arousal and synaptic plasticity during learning, and gives the genetics of dyslexia a testable biological axis.
ER -