Title: Brain-wide structural connectivity alterations under the control of Alzheimer risk genes

Authors: Jingwen Yan; V. Vinesh Raja; Zhi Huang; Enrico Amico; Kwangsik Nho; Shiaofen Fang; Olaf Sporns; Yu-chien Wu; Andrew Saykin; Joaquín Goñi; Li Shen

Addresses: Department of BioHealth Informatics, Indiana University Purdue University Indianapolis, 719 Indiana Ave, 46202, Indianapolis, USA ' Department of BioHealth Informatics, Indiana University Purdue University Indianapolis, 719 Indiana Ave, 46202, Indianapolis, USA ' Electrical and Computing Engineering, Indiana University Purdue University Indianapolis, 46202, Indianapolis, USA ' School of Industrial Engineering, Purdue Institute for Integrative Neuroscience, Purdue University, 47907, West-Lafayette, USA ' Radiology and Imaging Sciences, Indiana University School of Medicine, 46202, Indianapolis, USA ' Computer Science, Indiana University Purdue University Indianapolis, 46202, Indianapolis, USA ' Psychological and Brain Sciences, Indiana University, 47405, Bloomington, USA ' Radiology and Imaging Sciences, Indiana University School of Medicine, 46202, Indianapolis, USA ' Radiology and Imaging Sciences, Indiana University School of Medicine, 46202, Indianapolis, USA ' School of Industrial Engineering, Weldon School of Biomedical Engineering, Purdue Institute for Integrative Neuroscience, Purdue University, 47907, West-Lafayette, USA ' Biostatistics, Epidemiology and Informatics, University of Pennsylvania, 19104, Philadelphia, USA

Abstract: Alzheimer's disease is the most common form of brain dementia characterised by gradual loss of memory. Large-scale genome-wide association studies (GWASs) have identified some AD risk genes, but their relationship with the brain-wide network breakdown in AD remains unknown. Using the genotype and diffusion tensor imaging (DTI) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we performed a targeted genetic association analysis of three types of link measures, including fibre anisotropy, fibre length and density. For fair comparison, all link measures were normalised with zero mean and unit standard deviation. We focused on 34 AD risk SNPs identified in previous GWAS studies. After Bonferroni correction, rs10498633 in SLC24A4 was found to be significantly associated with anisotropy, total number and length of fibres. rs429358 in top AD risk gene APOE showed nominal significance of association with the density of fibres between subcortical and cerebellum regions.

Keywords: brain connectivity; imaging genetics association; Alzheimer's disease.

DOI: 10.1504/IJCBDD.2020.105098

International Journal of Computational Biology and Drug Design, 2020 Vol.13 No.1, pp.58 - 70

Received: 27 Jun 2018
Accepted: 27 Sep 2018

Published online: 13 Feb 2020 *

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