James P Boardman1, Andrew Walley2, Gareth Ball3, Petros Takousis4, Michelle L Krishnan3, Laurelle Hughes-Carre5, Paul Aljabar3, Ahmed Serag6, Caroline King5, Nazakat Merchant3, Latha Srinivasan5, Philippe Froguel7, Jo Hajnal3, Daniel Rueckert8, Serena Counsell3, A David Edwards3. 1. Medical Research Council/University of Edinburgh Centre for Reproductive Health, Edinburgh, United Kingdom; james.boardman@ed.ac.uk. 2. Departments of Genomics of Common Disease, School of Public Health,Molecular Genetics and Genomics, National Heart and Lung Institute. 3. Centre for the Developing Brain, King's College London, London, England, United Kingdom; 4. Departments of Genomics of Common Disease, School of Public Health. 5. Paediatrics, and. 6. The Advanced Pediatric Brain Imaging Research Laboratory, Children's National Medical Center, Washington, District of Columbia; and. 7. Departments of Genomics of Common Disease, School of Public Health,Centre National de la Recherche Scientifique-CNRS 8199, Lille 2 University, Paris, France. 8. Computing, Imperial College London, London, England, United Kingdom;
Abstract
BACKGROUND: The role of heritable factors in determining the common neurologic deficits seen after preterm birth is unknown, but the characteristic phenotype of neurocognitive, neuroanatomical, and growth abnormalities allows principled selection of candidate genes to test the hypothesis that common genetic variation modulates the risk for brain injury. METHODS: We collected an MRI-linked genomic DNA library from 83 preterm infants and genotyped tag single nucleotide polymorphisms in 13 relevant candidate genes. We used tract-based spatial statistics and deformation-based morphometry to examine the risks conferred by carriage of particular alleles at tag single nucleotide polymorphisms in a restricted number of genes and related these to the preterm cerebral endophenotype. RESULTS: Carriage of the minor allele at rs2518824 in the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) gene, which has been linked to neuronal migration and schizophrenia, and rs174576 in the fatty acid desaturase 2 gene, which encodes a rate-limiting enzyme for endogenous long chain polyunsaturated fatty acid synthesis and has been linked to intelligence, was associated with white matter abnormality measured in vivo using diffusion tensor imaging (P = .0009 and P = .0019, respectively). CONCLUSIONS: These results suggest that genetic variants modulate white matter injury after preterm birth, and known susceptibilities to neurologic status in later life may be exposed by the stress of premature exposure to the extrauterine environment.
BACKGROUND: The role of heritable factors in determining the common neurologic deficits seen after preterm birth is unknown, but the characteristic phenotype of neurocognitive, neuroanatomical, and growth abnormalities allows principled selection of candidate genes to test the hypothesis that common genetic variation modulates the risk for brain injury. METHODS: We collected an MRI-linked genomic DNA library from 83 preterm infants and genotyped tag single nucleotide polymorphisms in 13 relevant candidate genes. We used tract-based spatial statistics and deformation-based morphometry to examine the risks conferred by carriage of particular alleles at tag single nucleotide polymorphisms in a restricted number of genes and related these to the preterm cerebral endophenotype. RESULTS: Carriage of the minor allele at rs2518824 in the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) gene, which has been linked to neuronal migration and schizophrenia, and rs174576 in the fatty acid desaturase 2 gene, which encodes a rate-limiting enzyme for endogenous long chain polyunsaturated fatty acid synthesis and has been linked to intelligence, was associated with white matter abnormality measured in vivo using diffusion tensor imaging (P = .0009 and P = .0019, respectively). CONCLUSIONS: These results suggest that genetic variants modulate white matter injury after preterm birth, and known susceptibilities to neurologic status in later life may be exposed by the stress of premature exposure to the extrauterine environment.
Authors: Krystle A Frahm; Jacob K Waldman; Soumya Luthra; Anthony C Rudine; A Paula Monaghan-Nichols; Uma R Chandran; Donald B DeFranco Journal: Mol Cell Endocrinol Date: 2017-05-26 Impact factor: 4.102
Authors: Susan D Shenkin; Cyril Pernet; Thomas E Nichols; Jean-Baptiste Poline; Paul M Matthews; Aad van der Lugt; Clare Mackay; Linda Lanyon; Bernard Mazoyer; James P Boardman; Paul M Thompson; Nick Fox; Daniel S Marcus; Aziz Sheikh; Simon R Cox; Devasuda Anblagan; Dominic E Job; David Alexander Dickie; David Rodriguez; Joanna M Wardlaw Journal: Neuroimage Date: 2017-02-14 Impact factor: 6.556
Authors: Devasuda Anblagan; Mark E Bastin; Sarah Sparrow; Chinthika Piyasena; Rozalia Pataky; Emma J Moore; Ahmed Serag; Alastair Graham Wilkinson; Jonathan D Clayden; Scott I Semple; James P Boardman Journal: Neuroimage Clin Date: 2015-03-28 Impact factor: 4.881
Authors: Michelle L Krishnan; Zi Wang; Matt Silver; James P Boardman; Gareth Ball; Serena J Counsell; Andrew J Walley; Giovanni Montana; Anthony David Edwards Journal: Brain Behav Date: 2016-04-02 Impact factor: 2.708