title: Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children.
abstract: Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia.
authors.affiliation: Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany. Electronic address: skeide@cbs.mpg.de.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skeide
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, 04103 Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemiology and LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kirsten
authors.affiliation: Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany.
authors.forename: Indra
authors.initials: I
authors.lastname: Kraft
authors.affiliation: Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Rudower Chaussee 18, 12489 Berlin, Germany.
authors.forename: Gesa
authors.initials: G
authors.lastname: Schaadt
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, 04103 Leipzig, Germany.
authors.forename: Bent
authors.initials: B
authors.lastname: Müller
authors.affiliation: Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Neef
authors.affiliation: Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Brauer
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, 04103 Leipzig, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Wilcke
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, 04103 Leipzig, Germany; Translational Center for Regenerative Medicine, Philipp-Rosenthal-Straße 55, 04103 Leipzig, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Emmrich
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, 04103 Leipzig, Germany; Translational Center for Regenerative Medicine, Philipp-Rosenthal-Straße 55, 04103 Leipzig, Germany; Massachusetts General Hospital and Harvard Medical School, Neurovascular Regulation Laboratory, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.affiliation: Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig, Germany.
authors.forename: Angela D
authors.initials: AD
authors.lastname: Friederici
mesh_terms: D001364:Awareness / Q000502:physiology*; D001931:Brain Mapping; D002648:Child; D056324:Diffusion Tensor Imaging; D004410:Dyslexia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010700:Phonetics; D020641:Polymorphism, Single Nucleotide; D011594:Psychometrics; D011932:Reading; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology*