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.

Ingår i:Cerebral cortex (New York, N.Y. : 1991): Oxford University Press (OUP)31:2, s. 933-9481460-21991047-3211

Av författaren/redakt...: Zhang, J; Xia, K; Ahn, M; Jha, SC; Blanchett, R; Crowley, JJ; visa fler...; Szatkiewicz, JP; Zou, F; Zhu, H; Styner, M; Gilmore, JH; Knickmeyer, RC; visa färre...

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