Genome-wide supported dyslexia risk variant rs11100040 alters neural connectivity profiles affecting phonological awareness in children
Michael
Skeide1*,
Holger
Kirsten2, 3,
Indra
Kraft1,
Gesa
Schaadt1, 4,
Bent
Müller2,
Arndt
Wilcke2,
Jens
Brauer1,
Johannes
Boltze2, 3 and
Angela
Friederici1
-
1
Max Planck Institute for Human Cognitive and Brain Sciences, Germany
-
2
Fraunhofer Institute for Cell Therapy and Immunology, Germany
-
3
Universität Leipzig, Germany
-
4
Humboldt-Universität zu Berlin, Germany
Developmental dyslexia, one of the most common learning disorders, leads to severe difficulties in learning how to read and write. Prior imaging genetics studies have linked several dyslexia risk genes to alterations of either brain structure or brain function. However, coherent evidence for genetic contributions to both structural and functional neural phenotypes relevant for the specific deficits has not yet been provided. In the present experiment, 10 dyslexia-associated single nucleotide polymorphisms impacting the genes KIAA0319, DCDC2, DYX1C1and SLC2A3 were genotyped in a sample of 9- to 12-year-old children. Additionally, the children underwent diffusion-weighted imaging and resting state functional magnetic resonance imaging as well as phonological awareness and spelling assessment. We demonstrate that rs11100040, a modifier of SLC2A3, affects the fractional anisotropy (FA) of the left arcuate fasciculus (AF). Furthermore, we provide evidence that rs11100040 alters the correlations of hemodynamic time series within fronto-temporal termination areas of the AF already at resting state in the absence of any linguistic stimulation. However, rs11100040 turned out to be a stronger predictor of brain function than of brain structure. The individual phonological awareness was predicted by the FA phenotype when accounting for the individual functional connectivity as a mediating phenotype. Phonological awareness was in turn associated with a retrospectively classified risk of DD. These results go beyond previous work by identifying a link between a DD risk genotype and a phonological awareness phenotype which depends on tightly interrelated brain-structural and brain-functional phenotypes.
Keywords:
Dyslexia,
DTI,
functional connectivity,
imaging genetics,
Arcuate Fasciculus,
fractional anisotropy,
phonological awareness,
resting state fMRI,
risk gene
Conference:
XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014.
Presentation Type:
Poster
Topic:
Language
Citation:
Skeide
M,
Kirsten
H,
Kraft
I,
Schaadt
G,
Müller
B,
Wilcke
A,
Brauer
J,
Boltze
J and
Friederici
A
(2015). Genome-wide supported dyslexia risk variant rs11100040 alters neural connectivity profiles affecting phonological awareness in children.
Conference Abstract:
XII International Conference on Cognitive Neuroscience (ICON-XII).
doi: 10.3389/conf.fnhum.2015.217.00310
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Received:
19 Feb 2015;
Published Online:
24 Apr 2015.
*
Correspondence:
Dr. Michael Skeide, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, skeide@cbs.mpg.de