Evidence map›Paper›PMID 33372590›Full record

ArticleBMC genomics2020

Multivariate genome wide association and network analysis of subcortical imaging phenotypes in Alzheimer's disease.

Xianglian Meng, Jin Li, Qiushi Zhang, Feng Chen, Chenyuan Bian, Xiaohui Yao, Jingwen Yan, Zhe Xu, Shannon L Risacher, Andrew J Saykin and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC genomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Xianglian MengSchool of Computer Information & Engineering, Changzhou Institute of Technology, Changzhou, 213032, China.
Jin LiCollege of Automation, Harbin Engineering University, Harbin, 150001, China.
Qiushi ZhangSchool of Computer Science, Northeast Electric Power University, Jilin, 132012, China.
Feng ChenCollege of Automation, Harbin Engineering University, Harbin, 150001, China.
Chenyuan BianCollege of Automation, Harbin Engineering University, Harbin, 150001, China.
Xiaohui YaoDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Jingwen YanDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Zhe XuSchool of Computer Information & Engineering, Changzhou Institute of Technology, Changzhou, 213032, China.
Shannon L RisacherDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Andrew J SaykinDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Hong LiangCollege of Automation, Harbin Engineering University, Harbin, 150001, China. lh@hrbeu.edu.cn.ORCID http://orcid.org/0000-0002-2590-7210
Li ShenDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. li.shen@pennmedicine.upenn.edu.
Alzheimer’s Disease Neuroimaging Initiative

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
Memory Circuitry in MCI and Early Alzheimer’s Disease Prodrome: Molecular DriversR01AG019771 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 2001 to 2021
$6.9M
Integrative Bioinformatics Approaches to Human Brain Genomics and ConnectomicsR01EB022574 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI SHEN, LI · 2016 to 2019
$1.9M
NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG10133NIA NIH HHS R01 AG019771NIA NIH HHS R01 AG19771NIA NIH HHS U01 AG024904NIBIB NIH HHS R01 EB022574
6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWAS) have identified many individual genes associated with brain imaging quantitative traits (QTs) in Alzheimer's disease (AD). However single marker level association discovery may not be able to address the underlying biological interactions with disease mechanism.

resultsIn this paper, we used the MGAS (Multivariate Gene-based Association test by extended Simes procedure) tool to perform multivariate GWAS on eight AD-relevant subcortical imaging measures. We conducted multiple iPINBPA (integrative Protein-Interaction-Network-Based Pathway Analysis) network analyses on MGAS findings using protein-protein interaction (PPI) data, and identified five Consensus Modules (CMs) from the PPI network. Functional annotation and network analysis were performed on the identified CMs. The MGAS yielded significant hits within APOE, TOMM40 and APOC1 genes, which were known AD risk factors, as well as a few new genes such as LAMA1, XYLB, HSD17B7P2, and NPEPL1. The identified five CMs were enriched by biological processes related to disorders such as Alzheimer's disease, Legionellosis, Pertussis, and Serotonergic synapse.

conclusionsThe statistical power of coupling MGAS with iPINBPA was higher than traditional GWAS method, and yielded new findings that were missed by GWAS. This study provides novel insights into the molecular mechanism of Alzheimer's Disease and will be of value to novel gene discovery and functional genomic studies.

Indexed as

Alzheimer DiseaseGenome-Wide Association StudyBrainGenetic Predisposition to DiseaseHumansPhenotypePolymorphism, Single NucleotideProtein Interaction MapsBrain imagingConsensus modulesiPINBPA network analysisMultivariate gene-based genome-wide analysis

Identifiers

PMID33372590
PMCPMC7771059

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.