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Genome-Wide Association Analysis of Neonatal White Matter Microstructure.


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.

SUBMITTER: Zhang J 

PROVIDER: S-EPMC7786356 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Genome-Wide Association Analysis of Neonatal White Matter Microstructure.

Zhang J J   Xia K K   Ahn M M   Jha S C SC   Blanchett R R   Crowley J J JJ   Szatkiewicz J P JP   Zou F F   Zhu H H   Styner M M   Gilmore J H JH   Knickmeyer R C RC  

Cerebral cortex (New York, N.Y. : 1991) 20210101 2


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  ...[more]

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