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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

ABSTRACT: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

SUBMITTER: Berndt SI 

PROVIDER: S-EPMC4786871 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

Berndt Sonja I SI   Camp Nicola J NJ   Skibola Christine F CF   Vijai Joseph J   Wang Zhaoming Z   Gu Jian J   Nieters Alexandra A   Kelly Rachel S RS   Smedby Karin E KE   Monnereau Alain A   Cozen Wendy W   Cox Angela A   Wang Sophia S SS   Lan Qing Q   Teras Lauren R LR   Machado Moara M   Yeager Meredith M   Brooks-Wilson Angela R AR   Hartge Patricia P   Purdue Mark P MP   Birmann Brenda M BM   Vajdic Claire M CM   Cocco Pierluigi P   Zhang Yawei Y   Giles Graham G GG   Zeleniuch-Jacquotte Anne A   Lawrence Charles C   Montalvan Rebecca R   Burdett Laurie L   Hutchinson Amy A   Ye Yuanqing Y   Call Timothy G TG   Shanafelt Tait D TD   Novak Anne J AJ   Kay Neil E NE   Liebow Mark M   Cunningham Julie M JM   Allmer Cristine C   Hjalgrim Henrik H   Adami Hans-Olov HO   Melbye Mads M   Glimelius Bengt B   Chang Ellen T ET   Glenn Martha M   Curtin Karen K   Cannon-Albright Lisa A LA   Diver W Ryan WR   Link Brian K BK   Weiner George J GJ   Conde Lucia L   Bracci Paige M PM   Riby Jacques J   Arnett Donna K DK   Zhi Degui D   Leach Justin M JM   Holly Elizabeth A EA   Jackson Rebecca D RD   Tinker Lesley F LF   Benavente Yolanda Y   Sala Núria N   Casabonne Delphine D   Becker Nikolaus N   Boffetta Paolo P   Brennan Paul P   Foretova Lenka L   Maynadie Marc M   McKay James J   Staines Anthony A   Chaffee Kari G KG   Achenbach Sara J SJ   Vachon Celine M CM   Goldin Lynn R LR   Strom Sara S SS   Leis Jose F JF   Weinberg J Brice JB   Caporaso Neil E NE   Norman Aaron D AD   De Roos Anneclaire J AJ   Morton Lindsay M LM   Severson Richard K RK   Riboli Elio E   Vineis Paolo P   Kaaks Rudolph R   Masala Giovanna G   Weiderpass Elisabete E   Chirlaque María-Dolores MD   Vermeulen Roel C H RCH   Travis Ruth C RC   Southey Melissa C MC   Milne Roger L RL   Albanes Demetrius D   Virtamo Jarmo J   Weinstein Stephanie S   Clavel Jacqueline J   Zheng Tongzhang T   Holford Theodore R TR   Villano Danylo J DJ   Maria Ann A   Spinelli John J JJ   Gascoyne Randy D RD   Connors Joseph M JM   Bertrand Kimberly A KA   Giovannucci Edward E   Kraft Peter P   Kricker Anne A   Turner Jenny J   Ennas Maria Grazia MG   Ferri Giovanni M GM   Miligi Lucia L   Liang Liming L   Ma Baoshan B   Huang Jinyan J   Crouch Simon S   Park Ju-Hyun JH   Chatterjee Nilanjan N   North Kari E KE   Snowden John A JA   Wright Josh J   Fraumeni Joseph F JF   Offit Kenneth K   Wu Xifeng X   de Sanjose Silvia S   Cerhan James R JR   Chanock Stephen J SJ   Rothman Nathaniel N   Slager Susan L SL  

Nature communications 20160309

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8  ...[more]

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