Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology.
In: NeuroImage, Jg. 244 (2021-12-01), S. 118603
Online
academicJournal
Zugriff:
Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.
Competing Interests: Declaration of Competing Interest Dr. Andreassen has received speaker's honorarium from Lundbeck, and is a consultant to HealthLytix. Dr. Dale is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict of interest policies. The other authors declare no competing interests.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
| Titel: |
Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology.
|
|---|---|
| Autor/in / Beteiligte Person: | Shadrin, AA ; Kaufmann, T ; van der Meer D ; Palmer, CE ; Makowski, C ; Loughnan, R ; Jernigan, TL ; Seibert, TM ; Hagler, DJ ; Smeland, OB ; Motazedi, E ; Chu, Y ; Lin, A ; Cheng, W ; Hindley, G ; Thompson, WK ; Fan, CC ; Holland, D ; Westlye, LT ; Frei, O ; Andreassen, OA ; Dale, AM |
| Link: | |
| Zeitschrift: | NeuroImage, Jg. 244 (2021-12-01), S. 118603 |
| Veröffentlichung: | Orlando, FL : Academic Press, c1992-, 2021 |
| Medientyp: | academicJournal |
| ISSN: | 1095-9572 (electronic) |
| DOI: | 10.1016/j.neuroimage.2021.118603 |
| Schlagwort: |
|
| Sonstiges: |
|