PMID- 34470669
OWN - NLM
STAT- MEDLINE
DCOM- 20220216
LR  - 20220811
IS  - 1756-994X (Electronic)
IS  - 1756-994X (Linking)
VI  - 13
IP  - 1
DP  - 2021 Sep 1
TI  - A transcriptome-wide association study of Alzheimer's disease using prediction 
      models of relevant tissues identifies novel candidate susceptibility genes.
PG  - 141
LID - 10.1186/s13073-021-00959-y [doi]
LID - 141
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified over 56 
      susceptibility loci associated with Alzheimer's disease (AD), but the genes 
      responsible for these associations remain largely unknown. METHODS: We performed 
      a large transcriptome-wide association study (TWAS) leveraging modified UTMOST 
      (Unified Test for MOlecular SignaTures) prediction models of ten brain tissues 
      that are potentially related to AD to discover novel AD genetic loci and putative 
      target genes in 71,880 (proxy) cases and 383,378 (proxy) controls of European 
      ancestry. RESULTS: We identified 53 genes with predicted expression associations 
      with AD risk at Bonferroni correction threshold (P value < 3.38 x 10(-6)). Based 
      on fine-mapping analyses, 21 genes at nine loci showed strong support for being 
      causal. CONCLUSIONS: Our study provides new insights into the etiology and 
      underlying genetic architecture of AD.
CI  - (c) 2021. The Author(s).
FAU - Sun, Yanfa
AU  - Sun Y
AD  - College of Life Science, Longyan University, Longyan, Fujian, 364012, People's 
      Republic of China.
AD  - Cancer Epidemiology Division, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, 
      96813, USA.
AD  - Fujian Provincial Key Laboratory for the Prevention and Control of Animal 
      Infectious Diseases and Biotechnology, Longyan, Fujian, 364012, People's Republic 
      of China.
AD  - Fujian Provincial Universities Key Laboratory of Preventive Veterinary Medicine 
      and Biotechnology (Longyan University), Longyan, Fujian, 364012, People's 
      Republic of China.
FAU - Zhu, Jingjing
AU  - Zhu J
AD  - Cancer Epidemiology Division, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, 
      96813, USA.
FAU - Zhou, Dan
AU  - Zhou D
AD  - Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
FAU - Canchi, Saranya
AU  - Canchi S
AD  - Department of Neurosciences, University of California, San Diego, La Jolla, CA, 
      92093, USA.
AD  - Veterans Affairs San Diego Healthcare System, San Diego, CA, 92093, USA.
FAU - Wu, Chong
AU  - Wu C
AD  - Department of Statistics, Florida State University, Tallahassee, FL, 32306, USA.
FAU - Cox, Nancy J
AU  - Cox NJ
AD  - Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
FAU - Rissman, Robert A
AU  - Rissman RA
AD  - Department of Neurosciences, University of California, San Diego, La Jolla, CA, 
      92093, USA.
AD  - Veterans Affairs San Diego Healthcare System, San Diego, CA, 92093, USA.
FAU - Gamazon, Eric R
AU  - Gamazon ER
AD  - Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
AD  - Clare Hall, University of Cambridge, Cambridge, CB3 9AL, UK.
AD  - MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, 
      Cambridge, CB2 0SL, UK.
FAU - Wu, Lang
AU  - Wu L
AD  - Cancer Epidemiology Division, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, 
      96813, USA. lwu@cc.hawaii.edu.
LA  - eng
GR  - R01 GM140287/GM/NIGMS NIH HHS/United States
GR  - R01 HG011138/HG/NHGRI NIH HHS/United States
GR  - P30 AG062429/AG/NIA NIH HHS/United States
GR  - R56 AG068026/AG/NIA NIH HHS/United States
GR  - R35 HG010718/HG/NHGRI NIH HHS/United States
GR  - U01 HG009086/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210901
PL  - England
TA  - Genome Med
JT  - Genome medicine
JID - 101475844
RN  - 0 (Resorcinols)
RN  - 0 (sohirnone A)
SB  - IM
MH  - *Alleles
MH  - Alzheimer Disease/*genetics/metabolism
MH  - Chromosome Mapping
MH  - Computational Biology/methods
MH  - Databases, Genetic
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - *Genetic Predisposition to Disease
MH  - *Genome-Wide Association Study
MH  - Humans
MH  - Models, Biological
MH  - Organ Specificity/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Resorcinols
MH  - Signal Transduction
MH  - *Transcriptome
PMC - PMC8408990
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Etiology
OT  - Susceptibility genes
OT  - Transcriptome-wide association study
COIS- Eric Gamazon receives an honorarium from the journal Circulation Research of the 
      American Heart Association as a member of the Editorial Board. The remaining 
      authors declare that they have no competing interests.
EDAT- 2021/09/03 06:00
MHDA- 2022/02/17 06:00
PMCR- 2021/09/01
CRDT- 2021/09/02 05:44
PHST- 2021/04/07 00:00 [received]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/02 05:44 [entrez]
PHST- 2021/09/03 06:00 [pubmed]
PHST- 2022/02/17 06:00 [medline]
PHST- 2021/09/01 00:00 [pmc-release]
AID - 10.1186/s13073-021-00959-y [pii]
AID - 959 [pii]
AID - 10.1186/s13073-021-00959-y [doi]
PST - epublish
SO  - Genome Med. 2021 Sep 1;13(1):141. doi: 10.1186/s13073-021-00959-y.