A rare missense variant of CASP7 is associated with familial late-onset Alzheimer's disease.
Association study
Enriched case-control
Gene-based analyses
Genome-wide association studies
Whole exome sequencing
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
19
03
2018
revised:
04
10
2018
accepted:
11
10
2018
pubmed:
7
12
2018
medline:
6
5
2020
entrez:
4
12
2018
Statut:
ppublish
Résumé
The genetic architecture of Alzheimer's disease (AD) is only partially understood. We conducted an association study for AD using whole sequence data from 507 genetically enriched AD cases (i.e., cases having close relatives affected by AD) and 4917 cognitively healthy controls of European ancestry (EA) and 172 enriched cases and 179 controls of Caribbean Hispanic ancestry. Confirmation of top findings from stage 1 was sought in two family-based genome-wide association study data sets and in a whole genome-sequencing data set comprising members from 42 EA and 115 Caribbean Hispanic families. We identified associations in EAs with variants in 12 novel loci. The most robust finding is a rare CASP7 missense variant (rs116437863; P = 2.44 × 10 Our study demonstrated that an enriched case design can strengthen genetic signals, thus allowing detection of associations that would otherwise be missed in a traditional case-control study.
Identifiants
pubmed: 30503768
pii: S1552-5260(18)33579-9
doi: 10.1016/j.jalz.2018.10.005
pmc: PMC6408965
mid: NIHMS1511645
pii:
doi:
Substances chimiques
CASP7 protein, human
EC 3.4.22.-
Caspase 7
EC 3.4.22.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
441-452Subventions
Organisme : NIA NIH HHS
ID : U01 AG049507
Pays : United States
Organisme : NIA NIH HHS
ID : UF1 AG047133
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG052354
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG049508
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052410
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG049505
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG058654
Pays : United States
Organisme : NIA NIH HHS
ID : U54 AG052427
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG058922
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052411
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL130114
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003991
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005681
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013846
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG056270
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG048927
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052409
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057519
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG015473
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG049506
Pays : United States
Investigateurs
Michelle Bellair
(M)
Huyen Dinh
(H)
Harsha Doddapeneni
(H)
Shannon Dugan-Perez
(S)
Adam English
(A)
Richard A Gibbs
(RA)
Yi Han
(Y)
Jianhong Hu
(J)
Joy Jayaseelan
(J)
Divya Kalra
(D)
Ziad Khan
(Z)
Viktoriya Korchina
(V)
Sandra Lee
(S)
Yue Liu
(Y)
Xiuping Liu
(X)
Donna Muzny
(D)
Waleed Nasser
(W)
William Salerno
(W)
Jireh Santibanez
(J)
Evette Skinner
(E)
Simon White
(S)
Kim Worley
(K)
Yiming Zhu
(Y)
Alexa Beiser
(A)
Yuning Chen
(Y)
Jaeyoon Chung
(J)
L Adrienne Cupples
(LA)
Anita DeStefano
(A)
Josee Dupuis
(J)
John Farrell
(J)
Lindsay Farrer
(L)
Daniel Lancour
(D)
Honghuang Lin
(H)
Ching Ti Liu
(CT)
Kathy Lunetta
(K)
Yiyi Ma
(Y)
Devanshi Patel
(D)
Chloe Sarnowski
(C)
Claudia Satizabal
(C)
Sudha Seshadri
(S)
Fangui Jenny Sun
(FJ)
Xiaoling Zhang
(X)
Seung Hoan Choi
(SH)
Eric Banks
(E)
Stacey Gabriel
(S)
Namrata Gupta
(N)
William Bush
(W)
Mariusz Butkiewicz
(M)
Jonathan Haines
(J)
Sandra Smieszek
(S)
Yeunjoo Song
(Y)
Sandra Barral
(S)
Phillip L De Jager
(PL)
Richard Mayeux
(R)
Christiane Reitz
(C)
Dolly Reyes
(D)
Giuseppe Tosto
(G)
Badri Vardarajan
(B)
Shahzad Amad
(S)
Najaf Amin
(N)
M Afran Ikram
(MA)
Sven van der Lee
(S)
Cornelia van Duijn
(C)
Ashley Vanderspek
(A)
Helena Schmidt
(H)
Reinhold Schmidt
(R)
Alison Goate
(A)
Manav Kapoor
(M)
Edoardo Marcora
(E)
Alan Renton
(A)
Kelley Faber
(K)
Tatiana Foroud
(T)
Michael Feolo
(M)
Adam Stine
(A)
Lenore J Launer
(LJ)
David A Bennett
(DA)
Li Charlie Xia
(LC)
Gary Beecham
(G)
Kara Hamilton-Nelson
(K)
James Jaworski
(J)
Brian Kunkle
(B)
Eden Martin
(E)
Margaret Pericak-Vance
(M)
Farid Rajabli
(F)
Michael Schmidt
(M)
Thomas H Mosley
(TH)
Laura Cantwell
(L)
Micah Childress
(M)
Yi-Fan Chou
(YF)
Rebecca Cweibel
(R)
Prabhakaran Gangadharan
(P)
Amanda Kuzma
(A)
Yuk Yee Leung
(YY)
Han-Jen Lin
(HJ)
John Malamon
(J)
Elisabeth Mlynarski
(E)
Adam Naj
(A)
Liming Qu
(L)
Gerard Schellenberg
(G)
Otto Valladares
(O)
Li-San Wang
(LS)
Weixin Wang
(W)
Nancy Zhang
(N)
Jennifer E Below
(JE)
Eric Boerwinkle
(E)
Jan Bressler
(J)
Myriam Fornage
(M)
Xueqiu Jian
(X)
Xiaoming Liu
(X)
Joshua C Bis
(JC)
Elizabeth Blue
(E)
Lisa Brown
(L)
Tyler Day
(T)
Michael Dorschner
(M)
Andrea R Horimoto
(AR)
Rafael Nafikov
(R)
Alejandro Q Nato
(AQ)
Pat Navas
(P)
Hiep Nguyen
(H)
Bruce Psaty
(B)
Kenneth Rice
(K)
Mohamad Saad
(M)
Harkirat Sohi
(H)
Timothy Thornton
(T)
Debby Tsuang
(D)
Bowen Wang
(B)
Ellen Wijsman
(E)
Daniela Witten
(D)
Lucinda Antonacci-Fulton
(L)
Elizabeth Appelbaum
(E)
Carlos Cruchaga
(C)
Robert S Fulton
(RS)
Daniel C Koboldt
(DC)
David E Larson
(DE)
Jason Waligorski
(J)
Richard K Wilson
(RK)
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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