Abstract
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
| Original language | English |
|---|---|
| Article number | 431 |
| Journal | Nature Communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2019 |
Bibliographical note
Publisher Copyright:© 2019, The Author(s).
ASJC Scopus subject areas
- Physics and Astronomy (all)
- Chemistry (all)
- Biochemistry, Genetics and Molecular Biology (all)
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In: Nature Communications, Vol. 10, No. 1, 431, 01.12.2019.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Shared heritability and functional enrichment across six solid cancers
AU - Jiang, Xia
AU - Finucane, Hilary K.
AU - Schumacher, Fredrick R.
AU - Schmit, Stephanie L.
AU - Tyrer, Jonathan P.
AU - Han, Younghun
AU - Michailidou, Kyriaki
AU - Lesseur, Corina
AU - Kuchenbaecker, Karoline B.
AU - Dennis, Joe
AU - Conti, David V.
AU - Casey, Graham
AU - Gaudet, Mia M.
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AU - Albanes, Demetrius
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AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Antoniou, Antonis C.
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AU - Arnold, Susanne M.
AU - Aronson, Kristan J.
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AU - Bandera, Elisa V.
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AU - Barnes, Daniel R.
AU - Batra, Jyotsna
AU - Beckmann, Matthias W.
AU - Benitez, Javier
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AU - Berndt, Sonja I.
AU - Bickeböller, Heike
AU - Bien, Stephanie A.
AU - Blomqvist, Carl
AU - Boccia, Stefania
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Bolla, Manjeet K.
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Brenton, James D.
AU - Brook, Mark N.
AU - Brunet, Joan
AU - Brunnström, Hans
AU - Buchanan, Daniel D.
AU - Burwinkel, Barbara
AU - Butzow, Ralf
AU - Cadoni, Gabriella
AU - Caldés, Trinidad
AU - Caligo, Maria A.
AU - Campbell, Ian
AU - Campbell, Peter T.
AU - Cancel-Tassin, Géraldine
AU - Cannon-Albright, Lisa
AU - Campa, Daniele
AU - Caporaso, Neil
AU - Carvalho, André L.
AU - Chan, Andrew T.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Chen, Chu
AU - Christiani, David C.
AU - Claes, Kathleen B.M.
AU - Claessens, Frank
AU - Clements, Judith
AU - Collée, J. Margriet
AU - Correa, Marcia Cruz
AU - Couch, Fergus J.
AU - Cox, Angela
AU - Cunningham, Julie M.
AU - Cybulski, Cezary
AU - Czene, Kamila
AU - Daly, Mary B.
AU - deFazio, Anna
AU - Devilee, Peter
AU - Diez, Orland
AU - Gago-Dominguez, Manuela
AU - Donovan, Jenny L.
AU - Dörk, Thilo
AU - Duell, Eric J.
AU - Dunning, Alison M.
AU - Dwek, Miriam
AU - Eccles, Diana M.
AU - Edlund, Christopher K.
AU - Edwards, Digna R.Velez
AU - Ellberg, Carolina
AU - Evans, D. Gareth
AU - Fasching, Peter A.
AU - Ferris, Robert L.
AU - Liloglou, Triantafillos
AU - Figueiredo, Jane C.
AU - Fletcher, Olivia
AU - Fortner, Renée T.
AU - Fostira, Florentia
AU - Franceschi, Silvia
AU - Friedman, Eitan
AU - Gallinger, Steven J.
AU - Ganz, Patricia A.
AU - Garber, Judy
AU - García-Sáenz, José A.
AU - Gayther, Simon A.
AU - Giles, Graham G.
AU - Godwin, Andrew K.
AU - Goldberg, Mark S.
AU - Goldgar, David E.
AU - Goode, Ellen L.
AU - Goodman, Marc T.
AU - Goodman, Gary
AU - Grankvist, Kjell
AU - Greene, Mark H.
AU - Gronberg, Henrik
AU - Gronwald, Jacek
AU - Guénel, Pascal
AU - Håkansson, Niclas
AU - Hall, Per
AU - Hamann, Ute
AU - Hamdy, Freddie C.
AU - Hamilton, Robert J.
AU - Hampe, Jochen
AU - Haugen, Aage
AU - Heitz, Florian
AU - Herrero, Rolando
AU - Hillemanns, Peter
AU - Hoffmeister, Michael
AU - Høgdall, Estrid
AU - Hong, Yun Chul
AU - Hopper, John L.
AU - Houlston, Richard
AU - Hulick, Peter J.
AU - Hunter, David J.
AU - Huntsman, David G.
AU - Idos, Gregory
AU - Imyanitov, Evgeny N.
AU - Ingles, Sue Ann
AU - Isaacs, Claudine
AU - Jakubowska, Anna
AU - James, Paul
AU - Jenkins, Mark A.
AU - Johansson, Mattias
AU - Johansson, Mikael
AU - John, Esther M.
AU - Joshi, Amit D.
AU - Kaneva, Radka
AU - Karlan, Beth Y.
AU - Kelemen, Linda E.
AU - Kühl, Tabea
AU - Khaw, Kay Tee
AU - Khusnutdinova, Elza
AU - Kibel, Adam S.
AU - Kiemeney, Lambertus A.
AU - Kim, Jeri
AU - Kjaer, Susanne K.
AU - Knight, Julia A.
AU - Kogevinas, Manolis
AU - Kote-Jarai, Zsofia
AU - Koutros, Stella
AU - Kristensen, Vessela N.
AU - Kupryjanczyk, Jolanta
AU - Lacko, Martin
AU - Lam, Stephan
AU - Lambrechts, Diether
AU - Landi, Maria Teresa
AU - Lazarus, Philip
AU - Le, Nhu D.
AU - Lee, Eunjung
AU - Lejbkowicz, Flavio
AU - Lenz, Heinz Josef
AU - Leslie, Goska
AU - Lessel, Davor
AU - Lester, Jenny
AU - Levine, Douglas A.
AU - Li, Li
AU - Li, Christopher I.
AU - Lindblom, Annika
AU - Lindor, Noralane M.
AU - Liu, Geoffrey
AU - Loupakis, Fotios
AU - Lubiński, Jan
AU - Maehle, Lovise
AU - Maier, Christiane
AU - Mannermaa, Arto
AU - Marchand, Loic Le
AU - Margolin, Sara
AU - May, Taymaa
AU - McGuffog, Lesley
AU - Meindl, Alfons
AU - Middha, Pooja
AU - Miller, Austin
AU - Milne, Roger L.
AU - MacInnis, Robert J.
AU - Modugno, Francesmary
AU - Montagna, Marco
AU - Moreno, Victor
AU - Moysich, Kirsten B.
AU - Mucci, Lorelei
AU - Muir, Kenneth
AU - Mulligan, Anna Marie
AU - Nathanson, Katherine L.
AU - Neal, David E.
AU - Ness, Andrew R.
AU - Neuhausen, Susan L.
AU - Nevanlinna, Heli
AU - Newcomb, Polly A.
AU - Newcomb, Lisa F.
AU - Nielsen, Finn Cilius
AU - Nikitina-Zake, Liene
AU - Nordestgaard, Børge G.
AU - Nussbaum, Robert L.
AU - Offit, Kenneth
AU - Olah, Edith
AU - Olama, Ali Amin Al
AU - Olopade, Olufunmilayo I.
AU - Olshan, Andrew F.
AU - Olsson, Håkan
AU - Osorio, Ana
AU - Pandha, Hardev
AU - Park, Jong Y.
AU - Pashayan, Nora
AU - Parsons, Michael T.
AU - Pejovic, Tanja
AU - Penney, Kathryn L.
AU - Peters, Wilbert H.M.
AU - Phelan, Catherine M.
AU - Phipps, Amanda I.
AU - Plaseska-Karanfilska, Dijana
AU - Pring, Miranda
AU - Prokofyeva, Darya
AU - Radice, Paolo
AU - Stefansson, Kari
AU - Ramus, Susan J.
AU - Raskin, Leon
AU - Rennert, Gad
AU - Rennert, Hedy S.
AU - van Rensburg, Elizabeth J.
AU - Riggan, Marjorie J.
AU - Risch, Harvey A.
AU - Risch, Angela
AU - Roobol, Monique J.
AU - Rosenstein, Barry S.
AU - Rossing, Mary Anne
AU - De Ruyck, Kim
AU - Saloustros, Emmanouil
AU - Sandler, Dale P.
AU - Sawyer, Elinor J.
AU - Schabath, Matthew B.
AU - Schleutker, Johanna
AU - Schmidt, Marjanka K.
AU - Setiawan, V. Wendy
AU - Shen, Hongbing
AU - Siegel, Erin M.
AU - Sieh, Weiva
AU - Singer, Christian F.
AU - Slattery, Martha L.
AU - Sorensen, Karina Dalsgaard
AU - Southey, Melissa C.
AU - Spurdle, Amanda B.
AU - Stanford, Janet L.
AU - Stevens, Victoria L.
AU - Stintzing, Sebastian
AU - Stone, Jennifer
AU - Sundfeldt, Karin
AU - Sutphen, Rebecca
AU - Swerdlow, Anthony J.
AU - Tajara, Eloiza H.
AU - Tangen, Catherine M.
AU - Tardon, Adonina
AU - Taylor, Jack A.
AU - Teare, M. Dawn
AU - Teixeira, Manuel R.
AU - Terry, Mary Beth
AU - Terry, Kathryn L.
AU - Thibodeau, Stephen N.
AU - Thomassen, Mads
AU - Bjørge, Line
AU - Tischkowitz, Marc
AU - Toland, Amanda E.
AU - Torres, Diana
AU - Townsend, Paul A.
AU - Travis, Ruth C.
AU - Tung, Nadine
AU - Tworoger, Shelley S.
AU - Ulrich, Cornelia M.
AU - Usmani, Nawaid
AU - Vachon, Celine M.
AU - Van Nieuwenhuysen, Els
AU - Vega, Ana
AU - Aguado-Barrera, Miguel Elías
AU - Wang, Qin
AU - Webb, Penelope M.
AU - Weinberg, Clarice R.
AU - Weinstein, Stephanie
AU - Weissler, Mark C.
AU - Weitzel, Jeffrey N.
AU - West, Catharine M.L.
AU - White, Emily
AU - Whittemore, Alice S.
AU - Wichmann, H. Erich
AU - Wiklund, Fredrik
AU - Winqvist, Robert
AU - Wolk, Alicja
AU - Woll, Penella
AU - Woods, Michael
AU - Wu, Anna H.
AU - Wu, Xifeng
AU - Yannoukakos, Drakoulis
AU - Zheng, Wei
AU - Zienolddiny, Shanbeh
AU - Ziogas, Argyrios
AU - Zorn, Kristin K.
AU - Lane, Jacqueline M.
AU - Saxena, Richa
AU - Thomas, Duncan
AU - Hung, Rayjean J.
AU - Diergaarde, Brenda
AU - McKay, James
AU - Peters, Ulrike
AU - Hsu, Li
AU - García-Closas, Montserrat
AU - Eeles, Rosalind A.
AU - Chenevix-Trench, Georgia
AU - Brennan, Paul J.
AU - Haiman, Christopher A.
AU - Simard, Jacques
AU - Easton, Douglas F.
AU - Gruber, Stephen B.
AU - Pharoah, Paul D.P.
AU - Price, Alkes L.
AU - Pasaniuc, Bogdan
AU - Amos, Christopher I.
AU - Kraft, Peter
AU - Lindström, Sara
N1 - Publisher Copyright: © 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
AB - Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
UR - http://www.scopus.com/inward/record.url?scp=85060528251&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060528251&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-08054-4
DO - 10.1038/s41467-018-08054-4
M3 - Article
C2 - 30683880
AN - SCOPUS:85060528251
VL - 10
IS - 1
M1 - 431
ER -