Post-GWAS multiomic functional investigation of the<i>TNIP1</i>locus in Alzheimer’s disease implicates mediation through<i>GPX3</i>

Panyard, Daniel J.; Reus, Lianne M.; Ali, Muhammad; Liu, Jihua; Deming, Yuetiva; Lu, Qiongshi; Kollmorgen, Gwendlyn; Suridjan, Ivonne; Wild, Norbert; Visser, Pieter Jelle; Bertram, Lars; Zetterberg, Henrik; Blennow, Kaj; Gobom, Johan; Western, Daniel; Sung, Yun Ju; Carlsson, Cynthia M.; Johnson, Sterling C.; Asthana, Sanjay; Cruchaga, Carlos; Tijms, Betty M.; Engelman, Corinne D.; Snyder, M

doi:10.1101/2022.11.04.22277162

2022

DOI: 10.1101/2022.11.04.22277162

|View full text |Cite

Preprint

Post-GWAS multiomic functional investigation of theTNIP1locus in Alzheimer’s disease implicates mediation throughGPX3

Daniel J. Panyard

Lianne M. Reus

Muhammad Ali

et al.

Abstract: The recently reportedTNIP1/GPX3locus from AD GWAS studies was investigated. Using proteomics and other functional omics data, we identified evidence for a functional mechanism linking variants in this locus to decreased CSF GPX3 levels as AD progresses, suggesting a new potential target for intervention.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Preprint1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Identification of novel associations of candidate loci with Alzheimer’s disease by leveraging the shared genetic basis with hippocampal volume

Jiang,

van der Lee,

Tesi

et al. 2024

Preprint

View full text Add to dashboard Cite

Objective: Alzheimer's disease (AD) is a complex neurodegenerative disorder with a considerable genetic contribution that remains not fully understood. The hippocampus plays a critical role in learning and memory, with its volume loss being a core hallmark of AD. Hippocampal volume also has a strong heritable component and its genetic underpinnings may help us to understand the complex biological mechanism underlying AD. Methods: We performed cross-trait analysis of exisiting GWAS data on late-onset AD and Hippocampal volumes using the conjunctional false discovery rate (conjFDR) framework to identify the specific shared genetic basis.For identified SNPs, we performed functional annotation and phenome-wide association studies (PheWAS). Results: Our cross-trait analyses identified 11 non-APOE lead genetic loci, of which 7 loci showed discordant directional effects (loci associated with decreased risk for AD and smaller hippocampal volumes, and vice versa). We found that SHARPIN and TNIP1 genes play a role in AD by affecting the hippocampal volumes. In addition, we observed 9 novel AD-hippocampus loci in genes previously implicated in AD (IGIP and ACE) and novel AD-genes (KCTD13, HINT1, SH3TC2, FAM53B, TPM1, IL34 and SSH2). Phenome-wide association study highlighted varying degrees of pleiotropy, including brain imaging measurements, white blood cell markers, red blood cell markers, and lipids in multiple shared loci. Conclusions: Our integrating GWAS study reveals a shared genetic basis between AD and hippocampal volumes. By integrating GWAS summary statistics for these two traits, we identified both novel and previously reported AD-hippocampus loci. Functional analysis highlights the roles of immune cells and lipid markers in the shared loci and traits, suggesting a shared neurobiological basis for both traits.

show abstract

Identification of novel associations of candidate loci with Alzheimer’s disease by leveraging the shared genetic basis with hippocampal volume

Jiang,

van der Lee,

Tesi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Post-GWAS multiomic functional investigation of theTNIP1locus in Alzheimer’s disease implicates mediation throughGPX3

Cited by 1 publication

References 47 publications

Identification of novel associations of candidate loci with Alzheimer’s disease by leveraging the shared genetic basis with hippocampal volume

Identification of novel associations of candidate loci with Alzheimer’s disease by leveraging the shared genetic basis with hippocampal volume

Contact Info

Product

Resources

About