title: Common genetic variants and risk of brain injury after preterm birth.
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.
authors.affiliation: Medical Research Council/University of Edinburgh Centre for Reproductive Health, Edinburgh, United Kingdom; james.boardman@ed.ac.uk.
authors.forename: James P
authors.initials: JP
authors.lastname: Boardman
authors.affiliation: Departments of Genomics of Common Disease, School of Public Health,Molecular Genetics and Genomics, National Heart and Lung Institute.
authors.forename: Andrew
authors.initials: A
authors.lastname: Walley
authors.affiliation: Centre for the Developing Brain, King's College London, London, England, United Kingdom;
authors.forename: Gareth
authors.initials: G
authors.lastname: Ball
authors.affiliation: Departments of Genomics of Common Disease, School of Public Health.
authors.forename: Petros
authors.initials: P
authors.lastname: Takousis
authors.affiliation: Centre for the Developing Brain, King's College London, London, England, United Kingdom;
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Krishnan
authors.affiliation: Paediatrics, and.
authors.forename: Laurelle
authors.initials: L
authors.lastname: Hughes-Carre
authors.affiliation: Centre for the Developing Brain, King's College London, London, England, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Aljabar
authors.affiliation: The Advanced Pediatric Brain Imaging Research Laboratory, Children's National Medical Center, Washington, District of Columbia; and.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Serag
authors.affiliation: Paediatrics, and.
authors.forename: Caroline
authors.initials: C
authors.lastname: King
authors.affiliation: Centre for the Developing Brain, King's College London, London, England, United Kingdom;
authors.forename: Nazakat
authors.initials: N
authors.lastname: Merchant
authors.affiliation: Paediatrics, and.
authors.forename: Latha
authors.initials: L
authors.lastname: Srinivasan
authors.affiliation: Departments of Genomics of Common Disease, School of Public Health,Centre National de la Recherche Scientifique-CNRS 8199, Lille 2 University, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.affiliation: Centre for the Developing Brain, King's College London, London, England, United Kingdom;
authors.forename: Jo
authors.initials: J
authors.lastname: Hajnal
authors.affiliation: Computing, Imperial College London, London, England, United Kingdom;
authors.forename: Daniel
authors.initials: D
authors.lastname: Rueckert
authors.affiliation: Centre for the Developing Brain, King's College London, London, England, United Kingdom;
authors.forename: Serena
authors.initials: S
authors.lastname: Counsell
authors.affiliation: Centre for the Developing Brain, King's College London, London, England, United Kingdom;
authors.forename: A David
authors.initials: AD
authors.lastname: Edwards
mesh_terms: D000483:Alleles; D051186:Armadillo Domain Proteins / Q000235:genetics; D001921:Brain / Q000473:pathology; D001925:Brain Damage, Chronic / Q000175:diagnosis* / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D058068:Endophenotypes; D044943:Fatty Acid Desaturases / Q000235:genetics; D015723:Gene Library; D056726:Genetic Association Studies; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis* / Q000235:genetics*; D007360:Intelligence / Q000235:genetics; D008279:Magnetic Resonance Imaging; D010750:Phosphoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics
chemical_list: C411307:ARVCF protein, human; D051186:Armadillo Domain Proteins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: genetics; magnetic resonance image; neonate; preterm