Genome-Wide Association Analysis of Neonatal White Matter Microstructure. (3rd October 2020)

• Record Type: Journal Article
• Authors: Zhang, J; Xia, K; Ahn, M; Jha, S C; Blanchett, R; Crowley, J J; Szatkiewicz, J P; Zou, F; Zhu, H; Styner, M; Gilmore, J H; Knickmeyer, R C
• Is Part Of: Cerebral cortex. Volume 31:Number 2(2021)
• Page Start: 933
• Page End: 948
• Publication Date: 2020-10-03
• Subjects: diffusion tensor imaging -- genome-wide association study -- infant -- magnetic resonance imaging; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhaa266
• Languages: English
• ISSNs: 1047-3211

Abstract

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.