Cited by 28Neonatal and fetal brain pathologyInfant Development and Preterm CareBirth, Development, and Health

Possible relationship between common genetic variation and white matter development in a pilot study of preterm infants

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Krishnan, Michelle L., Wang, Zi, Silver, Matt, Boardman, James P., Ball, Gareth, Counsell, Serena J., Walley, Andrew J., Montana, Giovanni +1 more·2016·Brain and Behavior

Abstract

Background: The consequences of preterm birth are a major public health concern with high rates of ensuing multisystem morbidity, and uncertain biological mechanisms. Common genetic variation may mediate vulnerability to the insult of prematurity and provide opportunities to predict and modify risk. Objective: To gain novel biological and therapeutic insights from the integrated analysis of magnetic resonance imaging and genetic data, informed by prior knowledge. Methods: We apply our previously validated pathway‐based statistical method and a novel network‐based method to discover sources of common genetic variation associated with imaging features indicative of structural brain damage. Results: Lipid pathways were highly ranked by Pathways Sparse Reduced Rank Regression in a model examining the effect of prematurity, and PPAR (peroxisome proliferator‐activated receptor) signaling was the highest ranked pathway once degree of prematurity was accounted for. Within the PPAR pathway, five genes were found by Graph Guided Group Lasso to be highly associated with the phenotype: aquaporin 7 (AQP 7), malic enzyme 1, NADP(+)‐dependent, cytosolic (ME 1), perilipin 1 (PLIN 1), solute carrier family 27 (fatty acid transporter), member 1 (SLC 27A1), and acetyl‐CoA acyltransferase 1 (ACAA 1). Expression of four of these (ACAA 1, AQP 7, ME 1, and SLC 27A1) is controlled by a common transcription factor, early growth response 4 (EGR‐4). Conclusions: This suggests an important role for lipid pathways in influencing development of white matter in preterm infants, and in particular a significant role for interindividual genetic variation in PPAR signaling.

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  • A separate study indicated a possible role for PPAR signaling in white matter development in preterm infants.

    “The results indicated a possible role for peroxisome proliferator-activated receptor (PPAR) signaling in white matter development in preterm infants”
  • That PPAR study is best considered a proof-of-concept study because of its very small sample size.

    “this study might best be considered a proof-of-concept study, given its very small sample size.”

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Authors
Krishnan, M. L., Wang, Z., Silver, M., Boardman, J. P., Ball, G., Counsell, S. J., Walley, A. J., Montana, G., & Edwards, A. D.
Affiliations
  • St Thomas' Hospital (GB)
  • London School of Hygiene & Tropical Medicine (GB)
  • MRC Centre for Reproductive Health (GB)
  • Imperial College London (GB)
Corresponding author
Krishnan, Michelle L.
Venue
Brain and Behavior
Publisher
Wiley
Published
2016-04-02
Volume
6
Issue
7
Pages
e00434-e00434
ISSN
  • 2157-9032 (ISSN-L)
  • 2162-3279
OpenAlex
W2328783496
Cited by
28
References
118
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 5 · 2018: 10 · 2017: 6
FWCI
8.14
Type
journal article
Language
en
Open access
Locations
  • Brain and Behavior (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, cc-by)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • National Institute on Handicapped Research
  • Guy's and St Thomas' NHS Foundation Trust
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
preterm birth, white matter development, common genetic variants, PPAR signaling, lipid pathways, structural brain damage, AQP7, ME1, PLIN1, SLC27A1, gene expression, network-based methods, preterm infants
MeSH terms
Brain Injuries, Humans, Infant, Newborn, Infant, Premature, Phenotype, Pilot Projects, Genetic Variation, Polymorphism, Single Nucleotide, Diffusion Magnetic Resonance Imaging, Lipid Metabolism, White Matter

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