PMID- 36048437
OWN - NLM
STAT- MEDLINE
DCOM- 20230331
LR  - 20230613
IS  - 1758-535X (Electronic)
IS  - 1079-5006 (Linking)
VI  - 78
IP  - 4
DP  - 2023 Mar 30
TI  - Identification of 5 Potential Predictive Biomarkers for Alzheimer's Disease by 
      Integrating the Unified Test for Molecular Signatures and Weighted Gene 
      Coexpression Network Analysis.
PG  - 653-658
LID - 10.1093/gerona/glac179 [doi]
AB  - BACKGROUND: Previous transcriptome-wide association study (TWAS) has documented 
      21 genes associated with Alzheimer's disease (AD) risk, but the predictive 
      biomarkers remain unexplored. METHODS: TWAS leveraging the unified test for 
      molecular signatures (UTMOST) was performed in 75,000 cases and 420,000 controls 
      with 10 brain tissue gene expression references. Weighted gene coexpression 
      network analysis (WGCNA) was conducted in GSE5281 and GSE48350 data sets 
      containing 167 AD samples and 247 controls. Random forest (RF) analysis was 
      applied to screen the potential predictive biomarkers based on overlapping genes 
      identified by TWAS and WGCNA, followed by comprehensive bioinformatic analyses 
      with differential gene expression, functional enrichment, and correlation with 
      immune cells. A nomogram was established to verify the predictive power of the 
      identified biomarkers. RESULTS: TWAS revealed 78 candidate genes (p < 2.89 x 
      10-6). In WGCNA turquoise module, 3 718 AD-related genes were screened. RF 
      identified 5 predictive biomarkers (FAM71E1, DDB2, AP4M1, GPR4, DOC2A), which are 
      enriched in the global genome nucleotide excision repair pathway and associated 
      with immune cell designations "Natural.killer.T.cell," "Memory.B.cell," 
      "T.follicular.helper.cell," "Neutrophil," and "MDSC." The nomogram based on the 5 
      markers showed a high predictive power. CONCLUSION: Five potential predictive 
      biomarkers for AD were identified, providing new insights into the pathogenesis 
      and etiology of AD.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of The 
      Gerontological Society of America. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Zhou, Siquan
AU  - Zhou S
AD  - Healthy Food Evaluation Research Center, West China School of Public Health and 
      West China Fourth Hospital, Sichuan University, Chengdu, China.
AD  - Laboratory of Molecular Translational Medicine, Center for Translational 
      Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and 
      Children (Sichuan University), Ministry of Education, Department of Pediatrics, 
      West China Second University Hospital, Sichuan University, Chengdu, China.
FAU - Ma, Guochen
AU  - Ma G
AD  - Healthy Food Evaluation Research Center, West China School of Public Health and 
      West China Fourth Hospital, Sichuan University, Chengdu, China.
FAU - Luo, Hang
AU  - Luo H
AD  - Healthy Food Evaluation Research Center, West China School of Public Health and 
      West China Fourth Hospital, Sichuan University, Chengdu, China.
FAU - Shan, Shufang
AU  - Shan S
AD  - Laboratory of Molecular Translational Medicine, Center for Translational 
      Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and 
      Children (Sichuan University), Ministry of Education, Department of Pediatrics, 
      West China Second University Hospital, Sichuan University, Chengdu, China.
FAU - Xiong, Jingyuan
AU  - Xiong J
AUID- ORCID: 0000-0001-9354-862X
AD  - Healthy Food Evaluation Research Center, West China School of Public Health and 
      West China Fourth Hospital, Sichuan University, Chengdu, China.
FAU - Cheng, Guo
AU  - Cheng G
AD  - Laboratory of Molecular Translational Medicine, Center for Translational 
      Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and 
      Children (Sichuan University), Ministry of Education, Department of Pediatrics, 
      West China Second University Hospital, Sichuan University, Chengdu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Gerontol A Biol Sci Med Sci
JT  - The journals of gerontology. Series A, Biological sciences and medical sciences
JID - 9502837
RN  - 0 (Biomarkers)
SB  - IM
CIN - J Gerontol A Biol Sci Med Sci. 2023 Mar 30;78(4):659-662. PMID: 36995007
MH  - Humans
MH  - *Gene Expression Profiling
MH  - *Alzheimer Disease/diagnosis/genetics
MH  - Transcriptome
MH  - Gene Regulatory Networks
MH  - Biomarkers
OTO - NOTNLM
OT  - AD
OT  - Random forests
OT  - TWAS
OT  - UTMOST
OT  - WGCNA
EDAT- 2022/09/02 06:00
MHDA- 2023/03/31 06:42
CRDT- 2022/09/01 11:32
PHST- 2022/05/11 00:00 [received]
PHST- 2023/03/31 06:42 [medline]
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/09/01 11:32 [entrez]
AID - 6681126 [pii]
AID - 10.1093/gerona/glac179 [doi]
PST - ppublish
SO  - J Gerontol A Biol Sci Med Sci. 2023 Mar 30;78(4):653-658. doi: 
      10.1093/gerona/glac179.