A telescope GWAS analysis strategy, based on SNPs-genes-pathways ensamble and on multivariate algorithms, to characterize late onset Alzheimer's disease.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 07 2020
21 07 2020
Historique:
received:
04
10
2019
accepted:
10
06
2020
entrez:
23
7
2020
pubmed:
23
7
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Genome-wide association studies (GWAS) have revealed a plethora of putative susceptibility genes for Alzheimer's disease (AD), with the sole exception of APOE gene unequivocally validated in independent study. Considering that the etiology of complex diseases like AD could depend on functional multiple genes interaction network, here we proposed an alternative GWAS analysis strategy based on (i) multivariate methods and on a (ii) telescope approach, in order to guarantee the identification of correlated variables, and reveal their connections at three biological connected levels. Specifically as multivariate methods, we employed two machine learning algorithms and a genetic association test and we considered SNPs, Genes and Pathways features in the analysis of two public GWAS dataset (ADNI-1 and ADNI-2). For each dataset and for each feature we addressed two binary classifications tasks: cases vs. controls and the low vs. high risk of developing AD considering the allelic status of APOEe4. This complex strategy allowed the identification of SNPs, genes and pathways lists statistically robust and meaningful from the biological viewpoint. Among the results, we confirm the involvement of TOMM40 gene in AD and we propose GRM7 as a novel gene significantly associated with AD.
Identifiants
pubmed: 32694537
doi: 10.1038/s41598-020-67699-8
pii: 10.1038/s41598-020-67699-8
pmc: PMC7374579
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
12063Subventions
Organisme : NIH HHS
ID : National Institutes of Health Grant U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062715
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002369
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Organisme : CIHR
Pays : Canada
Investigateurs
Michael W Weiner
(MW)
Paul Aisen
(P)
Ronald Petersen
(R)
Jack R Clifford
(JR)
William Jagust
(W)
John Q Trojanowki
(JQ)
Arthur W Toga
(AW)
Laurel Beckett
(L)
Robert C Green
(RC)
Andrew J Saykin
(AJ)
John Morris
(J)
Leslie M Shaw
(LM)
Zaven Khachaturian
(Z)
Greg Sorensen
(G)
Maria Carrillo
(M)
Lew Kuller
(L)
Marc Raichle
(M)
Steven Paul
(S)
Peter Davies
(P)
Howard Fillit
(H)
Franz Hefti
(F)
Davie Holtzman
(D)
M Marcel Mesulam
(MM)
William Potter
(W)
Peter Snyder
(P)
Tom Montine
(T)
Ronald G Thomas
(RG)
Michael Donohue
(M)
Sarah Walter
(S)
Tamie Sather
(T)
Gus Jiminez
(G)
Archana B Balasubramanian
(AB)
Jennifer Mason
(J)
Iris Sim
(I)
Danielle Harvey
(D)
Matthew Bernstein
(M)
Nick Fox
(N)
Paul Thompson
(P)
Norbert Schuff
(N)
Charles DeCarli
(C)
Bret Borowski
(B)
Jeff Gunter
(J)
Matt Senjem
(M)
Prashanthi Vemuri
(P)
David Jones
(D)
Kejal Kantarci
(K)
Chad Ward
(C)
Robert A Koeppe
(RA)
Norm Foster
(N)
Eric M Reiman
(EM)
Kewei Chen
(K)
Chet Mathis
(C)
Susan Landau
(S)
Nigel J Cairns
(NJ)
Erin Householder
(E)
Lisa Taylor-Reinwald
(L)
Virginia Lee
(V)
Magdalena Korecka
(M)
Michal Figurski
(M)
Karen Crawford
(K)
Scott Neu
(S)
Tatiana M Foroud
(TM)
Steven Potkin
(S)
Li Shen
(L)
Kelley Faber
(K)
Sungeun Kim
(S)
Lean Tha
(L)
Richard Frank
(R)
John Hsiao
(J)
Jeffrey Kaye
(J)
Joseph Quinn
(J)
Lisa Silbert
(L)
Betty Lind
(B)
Raina Carter
(R)
Sara Dolen
(S)
Beau Ances
(B)
Maria Carroll
(M)
Mary L Creech
(ML)
Erin Franklin
(E)
Mark A Mintun
(MA)
Stacy Schneider
(S)
Angela Oliver
(A)
Lon S Schneider
(LS)
Sonia Pawluczyk
(S)
Mauricio Beccera
(M)
Liberty Teodoro
(L)
Bryan M Spann
(BM)
James Brewer
(J)
Helen Vanderswag
(H)
Adam Fleisher
(A)
Daniel Marson
(D)
Randall Griffith
(R)
David Clark
(D)
David Geldmacher
(D)
John Brockington
(J)
Erik Roberson
(E)
Marissa Natelson Love
(MN)
Judith L Heidebrink
(JL)
Joanne L Lord
(JL)
Sara S Mason
(SS)
Colleen S Albers
(CS)
David Knopman
(D)
Kris Johnson
(K)
Hillel Grossman
(H)
Effie Mitsis
(E)
Raj C Shah
(RC)
Leyla de Toledo-Morrell
(L)
Rachelle S Doody
(RS)
Javier Villanueva-Meyer
(J)
Munir Chowdhury
(M)
Susan Rountree
(S)
Mimi Dang
(M)
Ranjan Duara
(R)
Daniel Varon
(D)
Maria T Greig
(MT)
Peggy Roberts
(P)
Yaakov Stern
(Y)
Lawrence S Honig
(LS)
Karen L Bell
(KL)
Marilyn Albert
(M)
Chiadi Onyike
(C)
Daniel D'Agostino
(D)
Stephanie Kielb
(S)
James E Galvin
(JE)
Brittany Cerbone
(B)
Christina A Michel
(CA)
Dana M Pogorelec
(DM)
Henry Rusinek
(H)
Mony J de Leon
(MJ)
Lidia Glodzik
(L)
Susan De Santi
(S)
Kyle Womack
(K)
Dana Mathews
(D)
Mary Quiceno
(M)
P Murali Doraiswamy
(PM)
Jeffrey R Petrella
(JR)
Salvador Borges-Neto
(S)
Terence Z Wong
(TZ)
Edward Coleman
(E)
Allan I Levey
(AI)
James J Lah
(JJ)
Janet S Cella
(JS)
Jeffrey M Burns
(JM)
Russell H Swerdlow
(RH)
William M Brooks
(WM)
Steven E Arnold
(SE)
Jason H Karlawish
(JH)
David Wolk
(D)
Christopher M Clark
(CM)
Liana Apostolova
(L)
Kathleen Tingus
(K)
Ellen Woo
(E)
Daniel H S Silverman
(DHS)
Po H Lu
(PH)
George Bartzokis
(G)
Charles D Smith
(CD)
Greg Jicha
(G)
Peter Hardy
(P)
Partha Sinha
(P)
Elizabeth Oates
(E)
Gary Conrad
(G)
Neill R Graff-Radford
(NR)
Francine Parfitt
(F)
Tracy Kendall
(T)
Heather Johnson
(H)
Oscar L Lopez
(OL)
Mary Ann Oakley
(MA)
Donna M Simpson
(DM)
Martin R Farlow
(MR)
Ann Marie Hake
(AM)
Brandy R Matthews
(BR)
Jared R Brosch
(JR)
Scott Herring
(S)
Cynthia Hunt
(C)
Anton P Porsteinsson
(AP)
Bonnie S Goldstein
(BS)
Kim Martin
(K)
Kelly M Makino
(KM)
M Saleem Ismail
(MS)
Connie Brand
(C)
Ruth A Mulnard
(RA)
Gaby Thai
(G)
Catherine Mc-Adams-Ortiz
(C)
Christopher H van Dyck
(CH)
Richard E Carson
(RE)
Martha G MacAvoy
(MG)
Pradeep Varma
(P)
Howard Chertkow
(H)
Howard Bergman
(H)
Chris Hosein
(C)
Sandra Black
(S)
Bojana Stefanovic
(B)
Curtis Caldwell
(C)
Ging-Yuek Robin Hsiung
(GR)
Howard Feldman
(H)
Benita Mudge
(B)
Michele Assaly
(M)
Elizabeth Finger
(E)
Stephen Pasternack
(S)
Irina Rachisky
(I)
Dick Trost
(D)
Andrew Kertesz
(A)
Charles Bernick
(C)
Donna Munic
(D)
Kristine Lipowski
(K)
Masandra Weintraub
(M)
Borna Bonakdarpour
(B)
Diana Kerwin
(D)
Chuang-Kuo Wu
(CK)
Nancy Johnson
(N)
Carl Sadowsky
(C)
Teresa Villena
(T)
Raymond Scott Turner
(RS)
Kathleen Johnson
(K)
Brigid Reynolds
(B)
Reisa A Sperling
(RA)
Keith A Johnson
(KA)
Gad Marshall
(G)
Jerome Yesavage
(J)
Joy L Taylor
(JL)
Barton Lane
(B)
Allyson Rosen
(A)
Jared Tinklenberg
(J)
Marwan N Sabbagh
(MN)
Christine M Belden
(CM)
Sandra A Jacobson
(SA)
Sherye A Sirrel
(SA)
Neil Kowall
(N)
Ronald Killiany
(R)
Andrew E Budson
(AE)
Alexander Norbash
(A)
Patricia Lynn Johnson
(PL)
Thomas O Obisesan
(TO)
Saba Wolday
(S)
Joanne Allard
(J)
Alan Lerner
(A)
Paula Ogrocki
(P)
Curtis Tatsuoka
(C)
Parianne Fatica
(P)
Evan Fletcher
(E)
Pauline Maillard
(P)
John Olichney
(J)
Owen Carmichael
(O)
Smita Kittur
(S)
Michael Borrie
(M)
T-Y Lee
(TY)
Rob Bartha
(R)
Sterling Johnson
(S)
Sanjay Asthana
(S)
Cynthia M Carlsson
(CM)
Adrian Preda
(A)
Dana Nguyen
(D)
Pierre Tariot
(P)
Anna Burke
(A)
Nadira Trncic
(N)
Adam Fleisher
(A)
Stephanie Reeder
(S)
Vernice Bates
(V)
Horacio Capote
(H)
Michelle Rainka
(M)
Douglas W Scharre
(DW)
Maria Kataki
(M)
Anahita Adeli
(A)
Earl A Zimmerman
(EA)
Dzintra Celmins
(D)
Alice D Brown
(AD)
Godfrey D Pearlson
(GD)
Karen Blank
(K)
Karen Anderson
(K)
Laura A Flashman
(LA)
Marc Seltzer
(M)
Mary L Hynes
(ML)
Robert B Santulli
(RB)
Kaycee M Sink
(KM)
Leslie Gordineer
(L)
Jeff D Williamson
(JD)
Pradeep Garg
(P)
Franklin Watkins
(F)
Brian R Ott
(BR)
Henry Querfurth
(H)
Geoffrey Tremont
(G)
Stephen Salloway
(S)
Paul Malloy
(P)
Stephen Correia
(S)
Howard J Rosen
(HJ)
Bruce L Miller
(BL)
David Perry
(D)
Jacobo Mintzer
(J)
Kenneth Spicer
(K)
David Bachman
(D)
Elizabether Finger
(E)
Stephen Pasternak
(S)
Irina Rachinsky
(I)
John Rogers
(J)
Dick Drost
(D)
Nunzio Pomara
(N)
Raymundo Hernando
(R)
Antero Sarrael
(A)
Susan K Schultz
(SK)
Laura L Boles Ponto
(LLB)
Hyungsub Shim
(H)
Karen Ekstam Smith
(KE)
Norman Relkin
(N)
Gloria Chaing
(G)
Michael Lin
(M)
Lisa Ravdin
(L)
Amanda Smith
(A)
Balebail Ashok Raj
(BA)
Kristin Fargher
(K)
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