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GWAS Study

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.

Berndt SI, Skibola CF, Joseph V et al.

23770605 PubMed ID
GWAS Study Type
16427 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

BS
Berndt SI
SC
Skibola CF
JV
Joseph V
CN
Camp NJ
NA
Nieters A
WZ
Wang Z
CW
Cozen W
MA
Monnereau A
WS
Wang SS
KR
Kelly RS
LQ
Lan Q
TL
Teras LR
CN
Chatterjee N
CC
Chung CC
YM
Yeager M
BA
Brooks-Wilson AR
HP
Hartge P
PM
Purdue MP
BB
Birmann BM
AB
Armstrong BK
CP
Cocco P
ZY
Zhang Y
SG
Severi G
ZA
Zeleniuch-Jacquotte A
LC
Lawrence C
BL
Burdette L
YJ
Yuenger J
HA
Hutchinson A
JK
Jacobs KB
CT
Call TG
ST
Shanafelt TD
NA
Novak AJ
KN
Kay NE
LM
Liebow M
WA
Wang AH
SK
Smedby KE
AH
Adami HO
MM
Melbye M
GB
Glimelius B
CE
Chang ET
GM
Glenn M
CK
Curtin K
CL
Cannon-Albright LA
JB
Jones B
DW
Diver WR
LB
Link BK
WG
Weiner GJ
CL
Conde L
BP
Bracci PM
RJ
Riby J
HE
Holly EA
SM
Smith MT
JR
Jackson RD
TL
Tinker LF
BY
Benavente Y
BN
Becker N
BP
Boffetta P
BP
Brennan P
FL
Foretova L
MM
Maynadie M
MJ
McKay J
SA
Staines A
RK
Rabe KG
AS
Achenbach SJ
VC
Vachon CM
GL
Goldin LR
SS
Strom SS
LM
Lanasa MC
SL
Spector LG
LJ
Leis JF
CJ
Cunningham JM
WJ
Weinberg JB
MV
Morrison VA
CN
Caporaso NE
NA
Norman AD
LM
Linet MS
DR
De Roos AJ
ML
Morton LM
SR
Severson RK
RE
Riboli E
VP
Vineis P
KR
Kaaks R
TD
Trichopoulos D
MG
Masala G
WE
Weiderpass E
CM
Chirlaque MD
VR
Vermeulen RC
TR
Travis RC
GG
Giles GG
AD
Albanes D
VJ
Virtamo J
WS
Weinstein S
CJ
Clavel J
ZT
Zheng T
HT
Holford TR
OK
Offit K
ZA
Zelenetz A
KR
Klein RJ
SJ
Spinelli JJ
BK
Bertrand KA
LF
Laden F
GE
Giovannucci E
KP
Kraft P
KA
Kricker A
TJ
Turner J
VC
Vajdic CM
EM
Ennas MG
FG
Ferri GM
ML
Miligi L
LL
Liang L
SJ
Sampson J
CS
Crouch S
PJ
Park JH
NK
North KE
CA
Cox A
SJ
Snowden JA
WJ
Wright J
CA
Carracedo A
LC
Lopez-Otin C
BS
Bea S
SI
Salaverria I
MD
Martin-Garcia D
CE
Campo E
FJ
Fraumeni JF
DS
de Sanjose S
HH
Hjalgrim H
CJ
Cerhan JR
CS
Chanock SJ
RN
Rothman N
SS
Slager SL
Chapter II

Abstract

Summary of the research findings

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

2,179 European ancestry cases, 6,221 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

16427
Total Participants
GWAS
Study Type
Yes
Replicated
1,709 European ancestry cases, 6,318 European ancestry controls
Replication Participants
European
Ancestry
Finland, Sweden, U.S., Australia, Italy, Netherlands, Greece, Canada, Germany, U.K., Spain, New Zealand, France, Norway, Denmark
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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