Exploring Shared Pathogenesis of Alzheimer's Disease and Type 2 Diabetes Mellitus via Co-expression Networks Analysis
CURRENT ALZHEIMER RESEARCH
Authors: Zhu, Yukun; Ding, Xuelu; She, Zhaoyuan; Bai, Xue; Nie, Ziyang; Wang, Feng; Wang, Fei; Geng, Xin
Abstract
Background: Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (T2DM) have an increased incidence in modern society. Although increasing evidence has supported the close linkage between these two disorders, the inter-relational mechanisms remain to be fully elucidated. Objective The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and T2DM. Methods: We downloaded the microarray data of AD and T2DM from the Gene Expression Omnibus (GEO) database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis (WGCNA) to identify gene network modules related to AD and T2DM. Then, Gene Ontology (GO) and pathway enrichment analysis were performed on the common genes existing in the AD and T2DM related modules by clusterProfiler and DOSE package. Finally, we utilized the STRING database to construct the protein-protein interaction network and found out the hub genes in the network. Results: Our findings indicated that seven and four modules were the most significant with AD and T2DM, respectively. Functional enrichment analysis showed that AD and T2DM common genes were mainly enriched in signaling pathways such as circadian entrainment, phagosome, glutathione metabolism and synaptic vesicle cycle. Protein-protein interaction network construction identified 10 hub genes (CALM1, LRRK2, RBX1, SLC6A1, TXN, SNRPF, GJA1, VWF, LPL, AGT) in AD and T2DM shared genes. Conclusion: Our work identified common pathogenesis of AD and T2DM. These shared pathways might provide a novel idea for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosis and treatment of AD and T2DM.
Identification of Candidate Genes for Reactivity in Guzerat (Bos indicus) Cattle: A Genome-Wide Association Study
PLOS ONE
Authors: dos Santos, Fernanda Caroline; Campolina Diniz Peixoto, Maria Gabriela; de Souza Fonseca, Pablo Augusto; Avila Pires, Maria de Fatima; Ventura, Ricardo Vieira; Rosse, Izinara da Cruz; Tomita Bruneli, Frank Angelo; Machado, Marco Antonio; Santos Carvalho, Maria Raquel
Abstract
Temperament is fundamental to animal production due to its direct influence on the animalherdsman relationship. When compared to calm animals, the aggressive, anxious or fearful ones exhibit less weight gain, lower reproductive efficiency, decreased milk production and higher herd maintenance costs, all of which contribute to reduced profits. However, temperament is a trait that is complex and difficult to assess. Recently, a new quantitative system, REATEST (R), for assessing reactivity, a phenotype of temperament, was developed. Herein, we describe the results of a Genome-wide association study for reactivity, assessed using REATEST (R) with a sample of 754 females from five dual-purpose ( milk and meat production) Guzerat ( Bos indicus) herds. Genotyping was performed using a 50k SNP chip and a two-step mixed model approach ( Grammar-Gamma) with a one-by-one marker regression was used to identify QTLs. QTLs for reactivity were identified on chromosomes BTA1, BTA5, BTA14, and BTA25. Five intronic and two intergenic markers were significantly associated with reactivity. POU1F1, DRD3, VWA3A, ZBTB20, EPHA6, SNRPF and NTN4 were identified as candidate genes. Previous QTL reports for temperament traits, covering areas surrounding the SNPs/genes identified here, further corroborate these associations. The seven genes identified in the present study explain 20.5% of reactivity variance and give a better understanding of temperament biology.