Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.
To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.
Ferreira
Manuel A R
MA
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
O'Donovan
Michael C
MC
Meng
Yan A
YA
Jones
Ian R
IR
Ruderfer
Douglas M
DM
Jones
Lisa
L
Fan
Jinbo
J
Kirov
George
G
Perlis
Roy H
RH
Green
Elaine K
EK
Smoller
Jordan W
JW
Grozeva
Detelina
D
Stone
Jennifer
J
Nikolov
Ivan
I
Chambert
Kimberly
K
Hamshere
Marian L
ML
Nimgaonkar
Vishwajit L
VL
Moskvina
Valentina
V
Thase
Michael E
ME
Caesar
Sian
S
Sachs
Gary S
GS
Franklin
Jennifer
J
Gordon-Smith
Katherine
K
Ardlie
Kristin G
KG
Gabriel
Stacey B
SB
Fraser
Christine
C
Blumenstiel
Brendan
B
Defelice
Matthew
M
Breen
Gerome
G
Gill
Michael
M
Morris
Derek W
DW
Elkin
Amanda
A
Muir
Walter J
WJ
McGhee
Kevin A
KA
Williamson
Richard
R
MacIntyre
Donald J
DJ
MacLean
Alan W
AW
St
Clair David
CD
Robinson
Michelle
M
Van Beck
Margaret
M
Pereira
Ana C P
AC
Kandaswamy
Radhika
R
McQuillin
Andrew
A
Collier
David A
DA
Bass
Nicholas J
NJ
Young
Allan H
AH
Lawrence
Jacob
J
Ferrier
I Nicol
IN
Anjorin
Adebayo
A
Farmer
Anne
A
Curtis
David
D
Scolnick
Edward M
EM
McGuffin
Peter
P
Daly
Mark J
MJ
Corvin
Aiden P
AP
Holmans
Peter A
PA
Blackwood
Douglas H
DH
Gurling
Hugh M
HM
Owen
Michael J
MJ
Purcell
Shaun M
SM
Sklar
Pamela
P
Craddock
Nick
N
D017487:Ankyrins / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D002881:Chromosomes, Human, Pair 12; D002884:Chromosomes, Human, Pair 15; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide
C490613:ANK3 protein, human; D017487:Ankyrins; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type