Genome-Wide Association Analysis of Neonatal White Matter Microstructure.


Journal

Cerebral cortex (New York, N.Y. : 1991)
ISSN: 1460-2199
Titre abrégé: Cereb Cortex
Pays: United States
ID NLM: 9110718

Informations de publication

Date de publication:
05 01 2021
Historique:
received: 15 08 2019
revised: 15 07 2020
accepted: 16 08 2020
pubmed: 4 10 2020
medline: 8 1 2022
entrez: 3 10 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 33009551
pii: 5917453
doi: 10.1093/cercor/bhaa266
pmc: PMC7786356
doi:

Substances chimiques

PSMF1 protein, human 0
Proteasome Endopeptidase Complex EC 3.4.25.1

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

933-948

Subventions

Organisme : NICHD NIH HHS
ID : P50 HD103573
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH086633
Pays : United States

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

J Zhang (J)

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

K Xia (K)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

M Ahn (M)

Department of Mathematics and Statistics, University of Nevada, Reno, NV, USA.

S C Jha (SC)

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

R Blanchett (R)

Genetics and Genome Sciences Program, Michigan State University, East Lansing, MI, USA.

J J Crowley (JJ)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

J P Szatkiewicz (JP)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.

F Zou (F)

Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.

H Zhu (H)

Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.

M Styner (M)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

J H Gilmore (JH)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

R C Knickmeyer (RC)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA.
Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA.

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