Genome-Wide Association Analysis of Neonatal White Matter Microstructure

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.

Automated summary

This study on genetic influences on early white matter development in neonates identified a latent measure of white matter microstructure and a significant intronic SNP in PSMF1 on chromosome 20 that exceeded the conventional GWAS threshold. Additional loci near genes associated with axon growth and guidance, fasciculation, and myelination were also found.