The University of Southampton
×
Filter your search:
University of Southampton Institutional Repository

Letter abstract - Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's Disease

Letter abstract - Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's Disease
Letter abstract - Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's Disease
We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).
1061-4036
1088-1093
Harold, Denise
d37e566f-4ca4-49ae-8082-6368cc4c4b57
Abraham, Richard
6d9e6f37-9c75-424e-ad0a-db2f52b6930a
Hollingworth, Paul
da6d01af-40ef-41ea-8882-ae0480a46faf
Sims, Rebecca
9e087008-d8a2-404f-a926-01ea46051733
Gerrish, Amy
cce4042b-477c-4a05-8615-2c170d0d8d98
Hamshere, Marian L.
098bb481-ca91-4175-a616-604d2600a7c5
Pahwa, Jaspreet Sing
ce187ac1-df9b-462b-b7c2-74ddac9eb1a4
Moskvina, Valentina
4232124b-ef58-429b-86fe-60cc970a7bbe
Dowzell, Kimberley
d720595b-c0cc-461b-99b1-efea57ebcd7d
Williams, Amy
21f0d03f-c73d-400c-9eba-bacd9b869846
Jones, Nicola
f29d0a14-9e0f-4322-be94-84686ee5436c
Thomas, Charlene
8fd2a8af-5e97-4cf5-b25d-93f463f18c91
Stretton, Alexandra
ead70481-0ce1-4a42-84ae-74aab12456c3
Morgan, Angharad R.
f4367173-2c9b-48fd-afaf-af30867cfa8d
Lovestone, Simon
8c74cdb9-c6cc-4f60-8ad4-beaf5b526040
Powell, John
0616c5bf-0ce6-48ef-9b89-45a72529beb1
Proitsi, Petroula
eeedf604-e2fb-4e94-874c-8cd47927ce33
Lupton, Michelle K.
8f6a2135-25f6-465e-98b1-9b08d7a28450
Brayne, Carol
978cfad1-c7f6-4f79-aa1c-4f189eaaf035
Rubinsztein, David C.
c841997b-4a3f-4643-b215-0f206d29a39e
Gill, Michael
408d1dfa-5205-4e50-8130-7b26aa8288e8
Lawlor, Brian
b408add8-e531-4b05-b1ca-46f1dbf4f2a6
Lynch, Aoibhinn
d9df2d9c-340e-4671-ba02-5248b2bd0be2
Morgan, Kevin
f4a865c9-f8cc-443c-a2e7-3e3ac5a8cf85
Brown, Kristelle S.
ebf1765b-e9de-4518-8e97-673a3355b833
Passmore, Peter A.
7fd65294-53af-410a-9516-163ac0544742
Craig, David
23276bd6-127b-4565-950e-8f42d299bc2c
McGuinness, Bernadette
90a0a19e-ed7f-4fe0-8860-74ee73ff037f
Todd, Stephen
826c1117-8f6d-4435-aa40-f345509d7e6e
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Mann, David
30f8f3e8-a02a-4135-b193-c91ccdedf5a1
Smith, A. David
df633949-c1d9-461d-bb86-bceffa024adb
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Kehoe, Patrick G.
c3d54052-f508-4091-86ce-ec4727ef3c9a
Hardy, John
7d6a3558-4b3a-4c69-953f-3f8a7d162dca
Mead, Simon
1e29a17b-01fa-47b2-a868-1847a7d8f7f8
Fox, Nick
a4203994-de67-44ab-93b7-12cac76c9369
Rosser, Martin
16eea17e-1fa8-49f8-905e-2b14b76dbe68
Collinge, John
6ddeb930-e7e6-487a-a1d9-7f388443964b
Maier, Wolfgang
2c2c79ec-df0d-4496-a280-6d391c96a245
Jessen, Frank
053caca2-d254-4a74-94d4-8dd7b3f20547
Schurmann, Britta
145f3274-950d-4982-a386-32eaa029a29f
Van den Bussche, Hendrick
d4a5cc7e-5107-435e-a4d1-cde114b074e6
Heuser, Isabella
4f0c7b5b-43fc-4c4f-9db6-def1572de2b1
Kornhuber, Johannes
2bc6daf3-9962-4111-9337-0e0338342a28
Wiltfang, Jens
2b456866-4261-447d-a7f4-2b39616725a4
Dichgans, Martin
064116bb-7f62-4535-86d2-6f8cd337db5a
Frolich, Lutz
bff7e58d-8663-4322-ba8f-8c5703b47905
Hampel, Harald
26e6bc8c-8844-4b95-853f-c63121d6a5f4
Hull, Michael
fcc213e1-3dd7-4c40-809f-e499d3f421a0
Rujescu, Dan
40282832-f132-4339-ac61-191308eb3d2b
Goate, Alison M.
f225aee4-5ec9-4112-b55a-4627b94b642f
Kauwe, John S.
504464ef-ef14-4132-b502-dabac06cd1bf
Cruchaga, Carlos
f649f0f3-4901-4918-ae59-a6ab5cc5471e
Nowotny, Petra
2cb7a37a-615a-479d-8c74-4b1c1af82031
Morris, John C.
38ea6d64-a15a-4537-b085-71953386f52b
Mayo, Kevin
84095cd5-7145-4644-875c-62c880f6606c
Sleegers, Kristel
c4f6c4fb-753d-4896-8b42-8929b6f44f1e
Bettens, Karolien
b446122d-1fba-4664-a0de-b8139679808b
Engelborghs, Sebastiaan
da7e9a0f-58a6-4689-9232-5f67489672fc
De Deyn, Peter P.
cc2ab4f2-fa6f-488f-b08d-2a4fbc86b073
Van Broeckhoven, Christine
db56ffb6-a7f9-45d1-9469-3e4cd8153779
Livingston, Gill
ea18efb5-2f07-42a9-be5e-0d7b5b02f229
Bass, Nicholas J.
1275f389-7efb-4f52-b7b6-26e02ec8de65
Gurling, Hugh
6b9821bf-b62b-4ef0-93b2-f3da8f6ecca4
McQuillin, Andrew
abeb86f8-9d6e-4d89-868e-3392276e81ce
Gwilliam, Rhian
71dda979-6126-4d76-9789-d109b266cbfb
Deloukas, Panagiotis
b247a172-3acf-4639-bf24-addd0e2ab2bc
Al-Chalabi, Ammar
db16bbda-7684-49b4-9b2d-9799c7dba33c
Shaw, Christopher E.
ad432fe6-4928-445b-a3e1-aaba83c6a530
Tsolaki, Magda
afd2742e-f2e8-4342-9be6-713bcef24e22
Singleton, Andrew B.
66288e5c-8235-4eed-8989-2ff805343570
Guerreiro, Rita
256a6566-6010-4e8a-8f66-702efadda4ec
Muhleisen, Thomas W.
78f55aed-811d-499f-95b6-c38f1d9170e3
Nothen, Markus M.
fbdfe5f9-6a23-4645-8711-00512002ffbe
Moebus, Susanne
54158839-78d2-4d3b-942d-ead947806206
Jockel, Karl Heinz
4415d576-6383-4d3a-80a0-d9c6dbb0385e
Klopp, Norman
cf541817-fd4c-4d14-a495-47ead7514da2
Wichmann, H.Erich
7c8553ea-6e55-4952-9111-4f3926d7d232
Carrasquillo, Minerva M
f34951fb-698e-4380-a83b-40b3f263c204
Pankratz, V.Shane
158d8615-5e50-42ec-a0cc-8a8ad6c57308
Younkin, Steven G.
43cbe681-3b39-446d-8671-5e44c2cbd77d
Holmans, Peter A.
864bcef0-930e-4fa5-8d7d-0c2a45d7eb17
O'Donovan, Michael
a25656b0-89fd-44d1-9351-c1c67a9a1db8
Owen, Michael J.
0e3a340c-b3a3-4631-94f6-b3f50c0d50b1
Williams, Julie
4752662a-f68a-40fd-bb6a-015c53d73d27
Harold, Denise
d37e566f-4ca4-49ae-8082-6368cc4c4b57
Abraham, Richard
6d9e6f37-9c75-424e-ad0a-db2f52b6930a
Hollingworth, Paul
da6d01af-40ef-41ea-8882-ae0480a46faf
Sims, Rebecca
9e087008-d8a2-404f-a926-01ea46051733
Gerrish, Amy
cce4042b-477c-4a05-8615-2c170d0d8d98
Hamshere, Marian L.
098bb481-ca91-4175-a616-604d2600a7c5
Pahwa, Jaspreet Sing
ce187ac1-df9b-462b-b7c2-74ddac9eb1a4
Moskvina, Valentina
4232124b-ef58-429b-86fe-60cc970a7bbe
Dowzell, Kimberley
d720595b-c0cc-461b-99b1-efea57ebcd7d
Williams, Amy
21f0d03f-c73d-400c-9eba-bacd9b869846
Jones, Nicola
f29d0a14-9e0f-4322-be94-84686ee5436c
Thomas, Charlene
8fd2a8af-5e97-4cf5-b25d-93f463f18c91
Stretton, Alexandra
ead70481-0ce1-4a42-84ae-74aab12456c3
Morgan, Angharad R.
f4367173-2c9b-48fd-afaf-af30867cfa8d
Lovestone, Simon
8c74cdb9-c6cc-4f60-8ad4-beaf5b526040
Powell, John
0616c5bf-0ce6-48ef-9b89-45a72529beb1
Proitsi, Petroula
eeedf604-e2fb-4e94-874c-8cd47927ce33
Lupton, Michelle K.
8f6a2135-25f6-465e-98b1-9b08d7a28450
Brayne, Carol
978cfad1-c7f6-4f79-aa1c-4f189eaaf035
Rubinsztein, David C.
c841997b-4a3f-4643-b215-0f206d29a39e
Gill, Michael
408d1dfa-5205-4e50-8130-7b26aa8288e8
Lawlor, Brian
b408add8-e531-4b05-b1ca-46f1dbf4f2a6
Lynch, Aoibhinn
d9df2d9c-340e-4671-ba02-5248b2bd0be2
Morgan, Kevin
f4a865c9-f8cc-443c-a2e7-3e3ac5a8cf85
Brown, Kristelle S.
ebf1765b-e9de-4518-8e97-673a3355b833
Passmore, Peter A.
7fd65294-53af-410a-9516-163ac0544742
Craig, David
23276bd6-127b-4565-950e-8f42d299bc2c
McGuinness, Bernadette
90a0a19e-ed7f-4fe0-8860-74ee73ff037f
Todd, Stephen
826c1117-8f6d-4435-aa40-f345509d7e6e
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Mann, David
30f8f3e8-a02a-4135-b193-c91ccdedf5a1
Smith, A. David
df633949-c1d9-461d-bb86-bceffa024adb
Love, Seth
c8c00a86-ecf8-4f61-8377-254305bdbc02
Kehoe, Patrick G.
c3d54052-f508-4091-86ce-ec4727ef3c9a
Hardy, John
7d6a3558-4b3a-4c69-953f-3f8a7d162dca
Mead, Simon
1e29a17b-01fa-47b2-a868-1847a7d8f7f8
Fox, Nick
a4203994-de67-44ab-93b7-12cac76c9369
Rosser, Martin
16eea17e-1fa8-49f8-905e-2b14b76dbe68
Collinge, John
6ddeb930-e7e6-487a-a1d9-7f388443964b
Maier, Wolfgang
2c2c79ec-df0d-4496-a280-6d391c96a245
Jessen, Frank
053caca2-d254-4a74-94d4-8dd7b3f20547
Schurmann, Britta
145f3274-950d-4982-a386-32eaa029a29f
Van den Bussche, Hendrick
d4a5cc7e-5107-435e-a4d1-cde114b074e6
Heuser, Isabella
4f0c7b5b-43fc-4c4f-9db6-def1572de2b1
Kornhuber, Johannes
2bc6daf3-9962-4111-9337-0e0338342a28
Wiltfang, Jens
2b456866-4261-447d-a7f4-2b39616725a4
Dichgans, Martin
064116bb-7f62-4535-86d2-6f8cd337db5a
Frolich, Lutz
bff7e58d-8663-4322-ba8f-8c5703b47905
Hampel, Harald
26e6bc8c-8844-4b95-853f-c63121d6a5f4
Hull, Michael
fcc213e1-3dd7-4c40-809f-e499d3f421a0
Rujescu, Dan
40282832-f132-4339-ac61-191308eb3d2b
Goate, Alison M.
f225aee4-5ec9-4112-b55a-4627b94b642f
Kauwe, John S.
504464ef-ef14-4132-b502-dabac06cd1bf
Cruchaga, Carlos
f649f0f3-4901-4918-ae59-a6ab5cc5471e
Nowotny, Petra
2cb7a37a-615a-479d-8c74-4b1c1af82031
Morris, John C.
38ea6d64-a15a-4537-b085-71953386f52b
Mayo, Kevin
84095cd5-7145-4644-875c-62c880f6606c
Sleegers, Kristel
c4f6c4fb-753d-4896-8b42-8929b6f44f1e
Bettens, Karolien
b446122d-1fba-4664-a0de-b8139679808b
Engelborghs, Sebastiaan
da7e9a0f-58a6-4689-9232-5f67489672fc
De Deyn, Peter P.
cc2ab4f2-fa6f-488f-b08d-2a4fbc86b073
Van Broeckhoven, Christine
db56ffb6-a7f9-45d1-9469-3e4cd8153779
Livingston, Gill
ea18efb5-2f07-42a9-be5e-0d7b5b02f229
Bass, Nicholas J.
1275f389-7efb-4f52-b7b6-26e02ec8de65
Gurling, Hugh
6b9821bf-b62b-4ef0-93b2-f3da8f6ecca4
McQuillin, Andrew
abeb86f8-9d6e-4d89-868e-3392276e81ce
Gwilliam, Rhian
71dda979-6126-4d76-9789-d109b266cbfb
Deloukas, Panagiotis
b247a172-3acf-4639-bf24-addd0e2ab2bc
Al-Chalabi, Ammar
db16bbda-7684-49b4-9b2d-9799c7dba33c
Shaw, Christopher E.
ad432fe6-4928-445b-a3e1-aaba83c6a530
Tsolaki, Magda
afd2742e-f2e8-4342-9be6-713bcef24e22
Singleton, Andrew B.
66288e5c-8235-4eed-8989-2ff805343570
Guerreiro, Rita
256a6566-6010-4e8a-8f66-702efadda4ec
Muhleisen, Thomas W.
78f55aed-811d-499f-95b6-c38f1d9170e3
Nothen, Markus M.
fbdfe5f9-6a23-4645-8711-00512002ffbe
Moebus, Susanne
54158839-78d2-4d3b-942d-ead947806206
Jockel, Karl Heinz
4415d576-6383-4d3a-80a0-d9c6dbb0385e
Klopp, Norman
cf541817-fd4c-4d14-a495-47ead7514da2
Wichmann, H.Erich
7c8553ea-6e55-4952-9111-4f3926d7d232
Carrasquillo, Minerva M
f34951fb-698e-4380-a83b-40b3f263c204
Pankratz, V.Shane
158d8615-5e50-42ec-a0cc-8a8ad6c57308
Younkin, Steven G.
43cbe681-3b39-446d-8671-5e44c2cbd77d
Holmans, Peter A.
864bcef0-930e-4fa5-8d7d-0c2a45d7eb17
O'Donovan, Michael
a25656b0-89fd-44d1-9351-c1c67a9a1db8
Owen, Michael J.
0e3a340c-b3a3-4631-94f6-b3f50c0d50b1
Williams, Julie
4752662a-f68a-40fd-bb6a-015c53d73d27

Harold, Denise, Abraham, Richard, Hollingworth, Paul, Sims, Rebecca, Gerrish, Amy, Hamshere, Marian L., Pahwa, Jaspreet Sing, Moskvina, Valentina, Dowzell, Kimberley, Williams, Amy, Jones, Nicola, Thomas, Charlene, Stretton, Alexandra, Morgan, Angharad R., Lovestone, Simon, Powell, John, Proitsi, Petroula, Lupton, Michelle K., Brayne, Carol, Rubinsztein, David C., Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Morgan, Kevin, Brown, Kristelle S., Passmore, Peter A., Craig, David, McGuinness, Bernadette, Todd, Stephen, Holmes, Clive, Mann, David, Smith, A. David, Love, Seth, Kehoe, Patrick G., Hardy, John, Mead, Simon, Fox, Nick, Rosser, Martin, Collinge, John, Maier, Wolfgang, Jessen, Frank, Schurmann, Britta, Van den Bussche, Hendrick, Heuser, Isabella, Kornhuber, Johannes, Wiltfang, Jens, Dichgans, Martin, Frolich, Lutz, Hampel, Harald, Hull, Michael, Rujescu, Dan, Goate, Alison M., Kauwe, John S., Cruchaga, Carlos, Nowotny, Petra, Morris, John C., Mayo, Kevin, Sleegers, Kristel, Bettens, Karolien, Engelborghs, Sebastiaan, De Deyn, Peter P., Van Broeckhoven, Christine, Livingston, Gill, Bass, Nicholas J., Gurling, Hugh, McQuillin, Andrew, Gwilliam, Rhian, Deloukas, Panagiotis, Al-Chalabi, Ammar, Shaw, Christopher E., Tsolaki, Magda, Singleton, Andrew B., Guerreiro, Rita, Muhleisen, Thomas W., Nothen, Markus M., Moebus, Susanne, Jockel, Karl Heinz, Klopp, Norman, Wichmann, H.Erich, Carrasquillo, Minerva M, Pankratz, V.Shane, Younkin, Steven G., Holmans, Peter A., O'Donovan, Michael, Owen, Michael J. and Williams, Julie (2009) Letter abstract - Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's Disease. Nature Genetics, 41 (10), 1088-1093. (doi:10.1038/ng.440).

Record type: Article

Abstract

We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).

This record has no associated files available for download.

More information

Published date: 2009

Identifiers

Local EPrints ID: 73445
URI: http://eprints.soton.ac.uk/id/eprint/73445
DOI: doi:10.1038/ng.440
ISSN: 1061-4036
PURE UUID: 107d53ce-8a59-4923-88cf-797c429508cb
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

Catalogue record

Date deposited: 05 Mar 2010
Last modified: 14 Mar 2024 02:43

Export record

Altmetrics

Contributors

Author: Denise Harold
Author: Richard Abraham
Author: Paul Hollingworth
Author: Rebecca Sims
Author: Amy Gerrish
Author: Marian L. Hamshere
Author: Jaspreet Sing Pahwa
Author: Valentina Moskvina
Author: Kimberley Dowzell
Author: Amy Williams
Author: Nicola Jones
Author: Charlene Thomas
Author: Alexandra Stretton
Author: Angharad R. Morgan
Author: Simon Lovestone
Author: John Powell
Author: Petroula Proitsi
Author: Michelle K. Lupton
Author: Carol Brayne
Author: David C. Rubinsztein
Author: Michael Gill
Author: Brian Lawlor
Author: Aoibhinn Lynch
Author: Kevin Morgan
Author: Kristelle S. Brown
Author: Peter A. Passmore
Author: David Craig
Author: Bernadette McGuinness
Author: Stephen Todd
Author: Clive Holmes ORCID iD
Author: David Mann
Author: A. David Smith
Author: Seth Love
Author: Patrick G. Kehoe
Author: John Hardy
Author: Simon Mead
Author: Nick Fox
Author: Martin Rosser
Author: John Collinge
Author: Wolfgang Maier
Author: Frank Jessen
Author: Britta Schurmann
Author: Hendrick Van den Bussche
Author: Isabella Heuser
Author: Johannes Kornhuber
Author: Jens Wiltfang
Author: Martin Dichgans
Author: Lutz Frolich
Author: Harald Hampel
Author: Michael Hull
Author: Dan Rujescu
Author: Alison M. Goate
Author: John S. Kauwe
Author: Carlos Cruchaga
Author: Petra Nowotny
Author: John C. Morris
Author: Kevin Mayo
Author: Kristel Sleegers
Author: Karolien Bettens
Author: Sebastiaan Engelborghs
Author: Peter P. De Deyn
Author: Christine Van Broeckhoven
Author: Gill Livingston
Author: Nicholas J. Bass
Author: Hugh Gurling
Author: Andrew McQuillin
Author: Rhian Gwilliam
Author: Panagiotis Deloukas
Author: Ammar Al-Chalabi
Author: Christopher E. Shaw
Author: Magda Tsolaki
Author: Andrew B. Singleton
Author: Rita Guerreiro
Author: Thomas W. Muhleisen
Author: Markus M. Nothen
Author: Susanne Moebus
Author: Karl Heinz Jockel
Author: Norman Klopp
Author: H.Erich Wichmann
Author: Minerva M Carrasquillo
Author: V.Shane Pankratz
Author: Steven G. Younkin
Author: Peter A. Holmans
Author: Michael O'Donovan
Author: Michael J. Owen
Author: Julie Williams

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Library staff additional information
Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×