Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization

Lin, Siying, Zhang, Haoyang, Qi, Mengling, Cooper, David N. ORCID: https://orcid.org/0000-0002-8943-8484, Yang, Yuedong, Yang, Yuanhao and Zhao, Huiying 2023. Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization. NeuroImage 279 , 120325. 10.1016/j.neuroimage.2023.120325

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Abstract

Observational studies consistently disclose brain imaging-derived phenotypes (IDPs) as critical markers for early diagnosis of both brain disorders and cardiovascular diseases. However, it remains unclear about the shared genetic landscape between brain IDPs and the risk of brain disorders and cardiovascular diseases, restricting the applications of potential diagnostic techniques through brain IDPs. Here, we reported genetic correlations and putative causal relationships between 921 brain IDPs, 20 brain disorders and six cardiovascular diseases by leveraging their large-scale genome-wide association study (GWAS) summary statistics. Applications of Mendelian randomization (MR) identified significant putative causal effects of multiple region-specific brain IDPs in relation to the increased risks for amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), autism spectrum disorder (ASD) and schizophrenia (SCZ). We also found brain IDPs specifically from temporal lobe as a putatively causal consequence of hypertension. The genome-wide colocalization analysis identified three genomic regions in which MDD, ASD and SCZ colocalized with the brain IDPs, and two novel SNPs to be associated with ASD, SCZ, and multiple brain IDPs. Furthermore, we identified a list of candidate genes involved in the shared genetics underlying pairs of brain IDPs and MDD, ASD, SCZ, ALS and hypertension. Our results provide novel insights into the genetic relationships between brain disorders and cardiovascular diseases and brain IDP, which may server as clues for using brain IDPs to predict risks of diseases.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2023-08-11
Publisher:	Elsevier
ISSN:	1053-8119
Date of First Compliant Deposit:	21 August 2023
Date of Acceptance:	11 August 2023
Last Modified:	22 Aug 2023 03:09
URI:	https://orca.cardiff.ac.uk/id/eprint/161969

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