Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 868-876 |
Number of pages | 9 |
Journal | Nature Genetics |
Volume | 45 |
Issue number | 8 |
DOIs | |
Publication status | Published - 1 Jan 2013 |
Externally published | Yes |
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In: Nature Genetics, Vol. 45, No. 8, 01.01.2013, p. 868-876.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
AU - Berndt, Sonja I.
AU - Skibola, Christine F.
AU - Joseph, Vijai
AU - Camp, Nicola J.
AU - Nieters, Alexandra
AU - Wang, Zhaoming
AU - Cozen, Wendy
AU - Monnereau, Alain
AU - Wang, Sophia S.
AU - Kelly, Rachel S.
AU - Lan, Qing
AU - Teras, Lauren R.
AU - Chatterjee, Nilanjan
AU - Chung, Charles C.
AU - Yeager, Meredith
AU - Brooks-Wilson, Angela R.
AU - Hartge, Patricia
AU - Purdue, Mark P.
AU - Birmann, Brenda M.
AU - Armstrong, Bruce K.
AU - Cocco, Pierluigi
AU - Zhang, Yawei
AU - Severi, Gianluca
AU - Zeleniuch-Jacquotte, Anne
AU - Lawrence, Charles
AU - Burdette, Laurie
AU - Yuenger, Jeffrey
AU - Hutchinson, Amy
AU - Jacobs, Kevin B.
AU - Call, Timothy G.
AU - Shanafelt, Tait D.
AU - Novak, Anne J.
AU - Kay, Neil E.
AU - Liebow, Mark
AU - Wang, Alice H.
AU - Smedby, Karin E.
AU - Adami, Hans Olov
AU - Melbye, Mads
AU - Glimelius, Bengt
AU - Chang, Ellen T.
AU - Glenn, Martha
AU - Curtin, Karen
AU - Cannon-Albright, Lisa A.
AU - Jones, Brandt
AU - Diver, W. Ryan
AU - Link, Brian K.
AU - Weiner, George J.
AU - Conde, Lucia
AU - Bracci, Paige M.
AU - Riby, Jacques
AU - Holly, Elizabeth A.
AU - Smith, Martyn T.
AU - Jackson, Rebecca D.
AU - Tinker, Lesley F.
AU - Benavente, Yolanda
AU - Becker, Nikolaus
AU - Boffetta, Paolo
AU - Brennan, Paul
AU - Foretova, Lenka
AU - Maynadie, Marc
AU - McKay, James
AU - Staines, Anthony
AU - Rabe, Kari G.
AU - Achenbach, Sara J.
AU - Vachon, Celine M.
AU - Goldin, Lynn R.
AU - Strom, Sara S.
AU - Lanasa, Mark C.
AU - Spector, Logan G.
AU - Leis, Jose F.
AU - Cunningham, Julie M.
AU - Weinberg, J. Brice
AU - Morrison, Vicki A.
AU - Caporaso, Neil E.
AU - Norman, Aaron D.
AU - Linet, Martha S.
AU - De Roos, Anneclaire J.
AU - Morton, Lindsay M.
AU - Severson, Richard K.
AU - Riboli, Elio
AU - Vineis, Paolo
AU - Kaaks, Rudolph
AU - Trichopoulos, Dimitrios
AU - Masala, Giovanna
AU - Weiderpass, Elisabete
AU - Chirlaque, María Dolores
AU - Vermeulen, Roel C.H.
AU - Travis, Ruth C.
AU - Giles, Graham G.
AU - Albanes, Demetrius
AU - Virtamo, Jarmo
AU - Weinstein, Stephanie
AU - Clavel, Jacqueline
AU - Zheng, Tongzhang
AU - Holford, Theodore R.
AU - Offit, Kenneth
AU - Zelenetz, Andrew
AU - Klein, Robert J.
AU - Spinelli, John J.
AU - Bertrand, Kimberly A.
AU - Laden, Francine
AU - Giovannucci, Edward
AU - Kraft, Peter
AU - Kricker, Anne
AU - Turner, Jenny
AU - Vajdic, Claire M.
AU - Ennas, Maria Grazia
AU - Ferri, Giovanni M.
AU - Miligi, Lucia
AU - Liang, Liming
AU - Sampson, Joshua
AU - Crouch, Simon
AU - Park, Ju Hyun
AU - North, Kari E.
AU - Cox, Angela
AU - Snowden, John A.
AU - Wright, Josh
AU - Carracedo, Angel
AU - Lopez-Otin, Carlos
AU - Bea, Silvia
AU - Salaverria, Itziar
AU - Martin-Garcia, David
AU - Campo, Elias
AU - Fraumeni, Joseph F.
AU - De Sanjose, Silvia
AU - Hjalgrim, Henrik
AU - Cerhan, James R.
AU - Chanock, Stephen J.
AU - Rothman, Nathaniel
AU - Slager, Susan L.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84881023533&partnerID=8YFLogxK
U2 - 10.1038/ng.2652
DO - 10.1038/ng.2652
M3 - Article
C2 - 23770605
AN - SCOPUS:84881023533
SN - 1061-4036
VL - 45
SP - 868
EP - 876
JO - Nature Genetics
JF - Nature Genetics
IS - 8
ER -