Genome-Wide Association Analysis of Neonatal White Matter Microstructure

Cereb Cortex. 2021 Jan 5;31(2):933-948. doi: 10.1093/cercor/bhaa266.

Abstract

A better understanding of genetic influences on early white matter development could significantly advance our understanding of neurological and psychiatric conditions characterized by altered integrity of axonal pathways. We conducted a genome-wide association study (GWAS) of diffusion tensor imaging (DTI) phenotypes in 471 neonates. We used a hierarchical functional principal regression model (HFPRM) to perform joint analysis of 44 fiber bundles. HFPRM revealed a latent measure of white matter microstructure that explained approximately 50% of variation in our tractography-based measures and accounted for a large proportion of heritable variation in each individual bundle. An intronic SNP in PSMF1 on chromosome 20 exceeded the conventional GWAS threshold of 5 x 10-8 (p = 4.61 x 10-8). Additional loci nearing genome-wide significance were located near genes with known roles in axon growth and guidance, fasciculation, and myelination.

Keywords: diffusion tensor imaging; genome-wide association study; infant; magnetic resonance imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Axons / physiology
  • Chromosomes, Human, Pair 20 / genetics
  • Diffusion Magnetic Resonance Imaging
  • Diffusion Tensor Imaging
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Image Processing, Computer-Assisted
  • Infant
  • Infant, Newborn
  • Male
  • Myelin Sheath / physiology
  • Nerve Fibers / physiology
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Proteasome Endopeptidase Complex / genetics
  • Regression Analysis
  • White Matter / ultrastructure*

Substances

  • PSMF1 protein, human
  • Proteasome Endopeptidase Complex