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Research Paper|Volume 11, Issue 21|pp 9862—9874

Genome-wide association study identifies SIAH3 locus influencing the rate of ventricular enlargement in non-demented elders

Xian Li1, Shu-Guang Chu2, Xue-Ning Shen3, Xiao-He Hou4, Wei Xu4, Ya-Nan Ou4, Qiang Dong3, Lan Tan1, Jin-Tai Yu3
  • 1Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China
  • 2Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
  • 3Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • 4Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
* Equal contribution
# Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Received: August 16, 2019Accepted: October 29, 2019Published: November 11, 2019
https://doi.org/10.18632/aging.102435

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Ventricular enlargement occurs in several neurodegenerative and psychiatric diseases. A large genome-wide association study (GWAS) has identified seven loci associated with ventricular volume. The rate of ventricular enlargement increased in the progression of disease from normal cognition to dementia. Here, we aimed to use the rate of ventricular enlargement as an endophenotype for the development and progression of neurodegenerative diseases to discover more common genetic variants. We performed a GWAS of the rate of ventricular enlargement using 507 nondemented non-Hispanic white participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Linear regression model was used to identify the association of the rate of ventricular enlargement with single nucleotide polymorphisms (SNPs) in PLINK software. The associations of genome-wide significant SNPs with other four phenotypes were further discussed. Two SNPs (rs11620312, P = 4.04×10−8; rs79174114, P = 4.28×10−8) within SIAH3 gene in linkage disequilibrium (LD) reached genome-wide significance for association with increased rate of ventricular enlargement. Some intergenic SNPs and SNPs within NKAIN2, TBC1D2, GALNT18, ABCC1 and SRCIN1 genes were identified as potential candidates. SIAH3 rs11620312-C carriers were associated with poor cognition and brain hypometabolism longitudinally. Our findings indicated that SIAH3 gene may have potential influence on the pathogenesis of neurodegenerative diseases.