Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes

Gyungah Jun; Adam C Naj; Gary W Beecham; Li-San Wang; Jacqueline Buros; Paul J Gallins; Joseph D Buxbaum; Nilufer Ertekin-Taner; M Daniele Fallin; Robert Friedland; Rivka Inzelberg; Patricia Kramer; Ekaterina Rogaeva; Peter St George-Hyslop; Laura B Cantwell; Beth A Dombroski; Andrew J Saykin; Eric M Reiman; David A Bennett; John C Morris; Kathryn L Lunetta; Eden R Martin; Thomas J Montine; Alison M Goate; Deborah Blacker; Debby W Tsuang; Duane Beekly; L Adrienne Cupples; Hakon Hakonarson; Walter Kukull; Tatiana M Foroud; Jonathan Haines; Richard Mayeux; Lindsay A Farrer; Margaret A Pericak-Vance; Gerard D Schellenberg

doi:10.1001/archneurol.2010.201

Back

Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes

Journal article

Open access

Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes

Gyungah Jun, Adam C Naj, Gary W Beecham, Li-San Wang, Jacqueline Buros, Paul J Gallins, Joseph D Buxbaum, Nilufer Ertekin-Taner, M Daniele Fallin, Robert Friedland, …

Archives of neurology (Chicago), Vol.67(12), pp.1473-1484

2010-12

DOI: https://doi.org/10.1001/archneurol.2010.201

PMID: 20697030

Abstract

Confidence Intervals

Genome-Wide Association Study

Meta-Analysis as Topic

Clusterin - genetics

Gene Frequency

Humans

Risk Factors

European Continental Ancestry Group

Genotype

Male

Monomeric Clathrin Assembly Proteins - genetics

Apolipoproteins E - genetics

Aged, 80 and over

Polymorphism, Single Nucleotide - genetics

Female

Aged

Receptors, Complement 3b - genetics

Alzheimer Disease - genetics

Odds Ratio

Cohort Studies

To determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) and whether risk for AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes. Association study of AD and CLU, PICALM, CR1, and APOE genotypes. Academic research institutions in the United States, Canada, and Israel. Seven thousand seventy cases with AD, 3055 with autopsies, and 8169 elderly cognitively normal controls, 1092 with autopsies, from 12 different studies, including white, African American, Israeli-Arab, and Caribbean Hispanic individuals. Unadjusted, CLU (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.96 for single-nucleotide polymorphism [SNP] rs11136000), CR1 (OR, 1.14; 95% CI, 1.07-1.22; SNP rs3818361), and PICALM (OR, 0.89; 95% CI, 0.84-0.94, SNP rs3851179) were associated with AD in white individuals. None were significantly associated with AD in the other ethnic groups. APOE ε4 was significantly associated with AD (ORs, 1.80-9.05) in all but 1 small white cohort and in the Arab cohort. Adjusting for age, sex, and the presence of at least 1 APOE ε4 allele greatly reduced evidence for association with PICALM but not CR1 or CLU. Models with the main SNP effect, presence or absence of APOE ε4, and an interaction term showed significant interaction between presence or absence of APOE ε4 and PICALM. We confirm in a completely independent data set that CR1, CLU, and PICALM are AD susceptibility loci in European ancestry populations. Genotypes at PICALM confer risk predominantly in APOE ε4-positive subjects. Thus, APOE and PICALM synergistically interact.

Files and links (1)

url

https://doi.org/10.1001/archneurol.2010.201View

Published (Version of record) Open

Metrics

20 Record Views

328 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.57 Alzheimer's Disease
Web Of Science research areas: Clinical Neurology
ESI research areas: Neuroscience & Behavior

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes
Creators: Gyungah Jun - Department of Medicine, Boston University, USA
Adam C Naj
Gary W Beecham
Li-San Wang
Jacqueline Buros
Paul J Gallins
Joseph D Buxbaum
Nilufer Ertekin-Taner
M Daniele Fallin
Robert Friedland
Rivka Inzelberg
Patricia Kramer
Ekaterina Rogaeva
Peter St George-Hyslop
Laura B Cantwell
Beth A Dombroski
Andrew J Saykin
Eric M Reiman
David A Bennett
John C Morris
Kathryn L Lunetta
Eden R Martin
Thomas J Montine
Alison M Goate
Deborah Blacker
Debby W Tsuang
Duane Beekly
L Adrienne Cupples
Hakon Hakonarson
Walter Kukull
Tatiana M Foroud
Jonathan Haines
Richard Mayeux
Lindsay A Farrer
Margaret A Pericak-Vance
Gerard D Schellenberg
Publication Details: Archives of neurology (Chicago), Vol.67(12), pp.1473-1484
Publisher: United States
Grant note: P50 AG005142-25 / NIA NIH HHS R01 AG009029 / NIA NIH HHS R01 AG025259-05 / NIA NIH HHS P50 AG005681-20 / NIA NIH HHS R01 AG016495-01 / NIA NIH HHS P50 AG008702 / NIA NIH HHS P50 AG023501 / NIA NIH HHS P01 AG010491 / NIA NIH HHS P30 AG028383-05 / NIA NIH HHS U01 AG016976-07 / NIA NIH HHS R01 AG031287-02 / NIA NIH HHS P50 AG005681 / NIA NIH HHS N01 HC025195 / NHLBI NIH HHS R01 AG031581 / NIA NIH HHS P30 AG010124-09 / NIA NIH HHS P50 AG005138-20 / NIA NIH HHS P50 AG005142-20 / NIA NIH HHS P01 AG03991 / NIA NIH HHS P50 AG016582-07S1 / NIA NIH HHS R01 AG 027944 / NIA NIH HHS R01AG020688 / NIA NIH HHS P50 AG016573 / NIA NIH HHS P01 AG019724 / NIA NIH HHS R01 NS017950-24 / NINDS NIH HHS P50 AG005136-28 / NIA NIH HHS R01 AG16495 / NIA NIH HHS R01 MH080295 / NIMH NIH HHS P50 AG005133-22 / NIA NIH HHS P50 AG005134 / NIA NIH HHS P50 AG008702-20 / NIA NIH HHS U01 AG032984-01 / NIA NIH HHS P30 AG010129-13 / NIA NIH HHS U01 AG006786 / NIA NIH HHS P50 AG005133-16 / NIA NIH HHS P30 AG028377-01 / NIA NIH HHS P50 AG023501-08 / NIA NIH HHS P50 AG016575 / NIA NIH HHS P50 AG005146-17S1 / NIA NIH HHS R01 NS017950-18 / NINDS NIH HHS U01 AG024904-07 / NIA NIH HHS P30 AG010124-15 / NIA NIH HHS K24 AG027841-05 / NIA NIH HHS K24 AG027841 / NIA NIH HHS R01 AG009029-09 / NIA NIH HHS R01 AG020688-05 / NIA NIH HHS P30 AG010129 / NIA NIH HHS P30 AG013854-04 / NIA NIH HHS R01 AG020688 / NIA NIH HHS R01 AG016495 / NIA NIH HHS P50 AG005131-16 / NIA NIH HHS P30 AG010124 / NIA NIH HHS K08 NS054811-06 / NINDS NIH HHS U01 AG016976 / NIA NIH HHS R01 AG017917 / NIA NIH HHS R01 HG02213 / NHGRI NIH HHS R01 MH080295-01A2 / NIMH NIH HHS R01 AG021547-05 / NIA NIH HHS P30 AG008051 / NIA NIH HHS P01 AG019724-10 / NIA NIH HHS U01 AG032984 / NIA NIH HHS P30 AG10161 / NIA NIH HHS R01 CA129769-03 / NCI NIH HHS R01 AG025259-01A2 / NIA NIH HHS P50 AG008671 / NIA NIH HHS R01 AG019757 / NIA NIH HHS P50 AG016574-09 / NIA NIH HHS R01 AG017173-04A2 / NIA NIH HHS P30 AG028377-05 / NIA NIH HHS P50 AG005131 / NIA NIH HHS P01 AG002219 / NIA NIH HHS P30 AG010129-09 / NIA NIH HHS R01 AG026916-01 / NIA NIH HHS U01 AG024904 / NIA NIH HHS P50 AG005681-23 / NIA NIH HHS P30 AG013854-10 / NIA NIH HHS U01 AG032984-03 / NIA NIH HHS RC2 AG036535-01 / NIA NIH HHS R01 AG008122-07 / NIA NIH HHS UL1 RR029893-01 / NCRR NIH HHS AG021547 / NIA NIH HHS U01 HG006375 / NHGRI NIH HHS P50 AG005146 / NIA NIH HHS RC2 AG036535-02 / NIA NIH HHS P50 AG016582 / NIA NIH HHS R01 AG032990-01A1 / NIA NIH HHS P50 AG023501-01 / NIA NIH HHS P50 AG016570 / NIA NIH HHS P50 AG005134-16 / NIA NIH HHS P50 AG025688-07 / NIA NIH HHS R01 MH080295-04 / NIMH NIH HHS P50 AG016570-01 / NIA NIH HHS P30 AG010161 / NIA NIH HHS P30 AG013854 / NIA NIH HHS P30 AG010129-19 / NIA NIH HHS P50 AG016582-10 / NIA NIH HHS P50 AG08671 / NIA NIH HHS R01 AG017173 / NIA NIH HHS P30 AG008017-15 / NIA NIH HHS P01 AG002219-22 / NIA NIH HHS P30 AG10133 / NIA NIH HHS P30 AG012300-06 / NIA NIH HHS R01 NS017950 / NINDS NIH HHS P50 AG005146-25 / NIA NIH HHS U01 AG016976-01 / NIA NIH HHS P50 AG008671-11 / NIA NIH HHS U01 AG10483 / NIA NIH HHS R01 AG033193 / NIA NIH HHS R01 CA129769-01A2 / NCI NIH HHS R01 AG021547-01A1 / NIA NIH HHS P50 AG005136-16 / NIA NIH HHS P50 AG016574-12 / NIA NIH HHS P30 AG008051-10 / NIA NIH HHS P30 AG010129-10 / NIA NIH HHS P50 AG16574 / NIA NIH HHS M01 RR000096-38 / NCRR NIH HHS U24 AG021886-02 / NIA NIH HHS P50 AG005133 / NIA NIH HHS P50 AG025688 / NIA NIH HHS P30 AG010161-14 / NIA NIH HHS P01 AG003991 / NIA NIH HHS AG025688 / NIA NIH HHS R01 AG008122-20 / NIA NIH HHS P30 AG013846-10 / NIA NIH HHS UL1 RR029893 / NCRR NIH HHS R01 AG019085-01A1 / NIA NIH HHS P50 AG016574-01 / NIA NIH HHS R01 AG016495-10 / NIA NIH HHS P50 AG005138-16 / NIA NIH HHS P30 AG028377 / NIA NIH HHS R01 AG027944-01A2 / NIA NIH HHS R01 AG027944 / NIA NIH HHS U01 AG010483-09 / NIA NIH HHS R01 AG030146 / NIA NIH HHS R01 AG031287 / NIA NIH HHS P30 AG008051-16 / NIA NIH HHS R37 AG015473 / NIA NIH HHS R01 AG031287-01A2 / NIA NIH HHS K08 NS054811 / NINDS NIH HHS K24 AG027841-01A1 / NIA NIH HHS U24 AG026395-05 / NIA NIH HHS P30 AG008017 / NIA NIH HHS R01 AG027944-04 / NIA NIH HHS R01 AG026916-04 / NIA NIH HHS UO1 AG16976 / NIA NIH HHS R01 AG019085 / NIA NIH HHS P30 AG019610-08 / NIA NIH HHS R01 AG031581-13 / NIA NIH HHS R01 AG033193-01 / NIA NIH HHS P01 AG002219-28 / NIA NIH HHS R01 AG041797 / NIA NIH HHS R01 AG021547 / NIA NIH HHS P50 AG05681 / NIA NIH HHS P50 AG016573-01A1 / NIA NIH HHS K01 AG030514 / NIA NIH HHS P30 AG028383-04 / NIA NIH HHS R37 AG015473-06 / NIA NIH HHS AG002219 / NIA NIH HHS P01 AG003991-16 / NIA NIH HHS R01 AG032990 / NIA NIH HHS MO1 RR00096 / NCRR NIH HHS P30 AG019610-01 / NIA NIH HHS P01 AG010491-14 / NIA NIH HHS R01 CA129769 / NCI NIH HHS P30 AG08051 / NIA NIH HHS P50 AG025688-01 / NIA NIH HHS P50 AG005142-26A16897 / NIA NIH HHS R01 AG026916 / NIA NIH HHS P50 AG005142 / NIA NIH HHS U01 AG024904-01 / NIA NIH HHS U24 AG026395 / NIA NIH HHS R01 AG17917 / NIA NIH HHS UL1 RR02777 / NCRR NIH HHS U24 AG021886 / NIA NIH HHS U01 AG032984-02 / NIA NIH HHS R01 AG08122 / NIA NIH HHS 081864 / Wellcome Trust U24-AG021886 / NIA NIH HHS P50 AG016574 / NIA NIH HHS P30 AG010133-15 / NIA NIH HHS RC2 AG036528 / NIA NIH HHS P50 AG008702-10 / NIA NIH HHS R01 AG017917-01A1 / NIA NIH HHS R01 AG033193-03 / NIA NIH HHS P30 AG013846-04 / NIA NIH HHS M01 RR000096 / NCRR NIH HHS UL1 RR029893-03 / NCRR NIH HHS R01 AG031581-10 / NIA NIH HHS RC2 AG036528-02 / NIA NIH HHS P30 AG019610 / NIA NIH HHS P50 AG016576 / NIA NIH HHS P50 AG005136 / NIA NIH HHS R01 AG017173-08 / NIA NIH HHS P50 AG008671-15 / NIA NIH HHS P30 AG10129 / NIA NIH HHS P50 AG005681-18 / NIA NIH HHS R01 HG002213-03 / NHGRI NIH HHS P01 AG019724-01A1 / NIA NIH HHS P50 AG005131-21 / NIA NIH HHS P50 AG016570-07 / NIA NIH HHS P50 AG005134-22 / NIA NIH HHS P50 AG005136-20 / NIA NIH HHS U01 AG006786-14 / NIA NIH HHS R01 AG008122 / NIA NIH HHS RC2 AG036535 / NIA NIH HHS N01HC25195 / NHLBI NIH HHS R01 AG009029-14 / NIA NIH HHS N01 HC-25195 / NHLBI NIH HHS R01 HG002213 / NHGRI NIH HHS RC2 AG036528-01 / NIA NIH HHS AG027944 / NIA NIH HHS R01 AG020688-01A2 / NIA NIH HHS U01AG06786 / NIA NIH HHS R37 AG015473-11 / NIA NIH HHS R01 HG002213-01 / NHGRI NIH HHS U01 AG010483-18 / NIA NIH HHS R01 AG015819 / NIA NIH HHS UL1 RR025777-04 / NCRR NIH HHS P30 AG012300-11 / NIA NIH HHS AG010491 / NIA NIH HHS P50 AG05131 / NIA NIH HHS AG019757 / NIA NIH HHS K01 AG030514-01A1 / NIA NIH HHS U01 AG010483 / NIA NIH HHS U24 AG021886-09 / NIA NIH HHS R01 AG019757-06 / NIA NIH HHS U19 AG010483 / NIA NIH HHS P01 AG003991-24 / NIA NIH HHS P30 AG028383 / NIA NIH HHS P30 AG010161-09 / NIA NIH HHS P30 AG012300 / NIA NIH HHS P30 AG008017-10 / NIA NIH HHS U24 AG026395-01 / NIA NIH HHS P30 AG010133 / NIA NIH HHS K01 AG030514-04 / NIA NIH HHS U24 AG056270 / NIA NIH HHS AG005138 / NIA NIH HHS P30 AG013846 / NIA NIH HHS R01 AG025259 / NIA NIH HHS P50 AG005138 / NIA NIH HHS R01 AG017917-05 / NIA NIH HHS U01 AG006786-24 / NIA NIH HHS M01 RR000096-47 / NCRR NIH HHS R01 AG037212 / NIA NIH HHS R01 AG019085-10 / NIA NIH HHS R01 AG019757-01A1 / NIA NIH HHS P50 AG016577 / NIA NIH HHS P01 AG010491-06A2 / NIA NIH HHS RC2AG036528 / NIA NIH HHS P50 AG016573-06 / NIA NIH HHS
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 20697030
Record Identifier: 991031560359302976