Shared heritability and functional enrichment across six solid cancers

Jiang, Xia; Finucane, Hilary K.; Schumacher, Fredrick R.; Schmit, Stephanie L.; Tyrer, Jonathan P.; Han, Younghun; Michailidou, Kyriaki; Lesseur, Corina; Kuchenbaecker, Karoline B.; Dennis, Joe; Conti, David V.; Casey, Graham; Gaudet, Mia M.; Huyghe, Jeroen R.; Albanes, Demetrius; Aldrich, Melinda C.; Andrew, Angeline S.; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Antonenkova, Natalia N.; Arnold, Susanne M.; Aronson, Kristan J.; Arun, Banu K.; Bandera, Elisa V.; Barkardottir, Rosa B.; Barnes, Daniel R.; Batra, Jyotsna; Beckmann, Matthias W.; Benitez, Javier; Benlloch, Sara; Berchuck, Andrew; Berndt, Sonja I.; Bickeboeller, Heike; Bien, Stephanie A.; Blomqvist, Carl; Boccia, Stefania; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Brauch, Hiltrud; Brenner, Hermann; Brenton, James D.; Brook, Mark N.; Brunet, Joan; Brunnstrom, Hans; Buchanan, Daniel D.; Burwinkel, Barbara; Butzow, Ralf; Cadoni, Gabriella; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Campbell, Peter T.; Cancel-Tassin, Geraldine; Cannon-Albright, Lisa; Campa, Daniele; Caporaso, Neil; Carvalho, Andre L.; Chan, Andrew T.; Chang-Claude, Jenny; Chanock, Stephen J.; Chen, Chu; Christiani, David C.; Claes, Kathleen B. M.; Claessens, Frank; Clements, Judith; Collee, J. Margriet; Correa, Marcia Cruz; Couch, Fergus J.; Cox, Angela; Cunningham, Julie M.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; defazio, Anna; Devilee, Peter; Diez, Orland; Gago-Dominguez, Manuela; Donovan, Jenny L.; Doerk, Thilo; Duell, Eric J.; Dunning, Alison M.; Dwek, Miriam; Eccles, Diana M.; Edlund, Christopher K.; Edwards, Digna R. Velez; Ellberg, Carolina; Evans, D. Gareth; Fasching, Peter A.; Ferris, Robert L.; Liloglou, Triantafillos; Figueiredo, Jane C.; Fletcher, Olivia; Fortner, Renee T.; Fostira, Florentia; Franceschi, Silvia; Friedman, Eitan; Gallinger, Steven J.; Ganz, Patricia A.; Garber, Judy; Garcia-Saenz, Jose A.; Gayther, Simon A.; Giles, Graham G.; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; Goode, Ellen L.; Goodman, Marc T.; Goodman, Gary; Grankvist, Kjell; Greene, Mark H.; Gronberg, Henrik; Gronwald, Jacek; Guenel, Pascal; Hakansson, Niclas; Hall, Per; Hamann, Ute; Hamdy, Freddie C.; Hamilton, Robert J.; Hampe, Jochen; Haugen, Aage; Heitz, Florian; Herrero, Rolando; Hillemanns, Peter; Hoffmeister, Michael; Hogdall, Estrid; Hong, Yun-Chul; Hopper, John L.; Houlston, Richard; Hulick, Peter J.; Hunter, David J.; Huntsman, David G.; Idos, Gregory; Imyanitov, Evgeny N.; Ingles, Sue Ann; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Jenkins, Mark A.; Johansson, Mattias; Johansson, Mikael; John, Esther M.; Joshi, Amit D.; Kaneva, Radka; Karlan, Beth Y.; Kelemen, Linda E.; Kuhl, Tabea; Khaw, Kay-Tee; Khusnutdinova, Elza; Kibel, Adam S.; Kiemeney, Lambertus A.; Kim, Jeri; Kjaer, Susanne K.; Knight, Julia A.; Kogevinas, Manolis; Kote-Jarai, Zsofia; Koutros, Stella; Kristensen, Vessela N.; Kupryjanczyk, Jolanta; Lacko, Martin; Lam, Stephan; Lambrechts, Diether; Landi, Maria Teresa; Lazarus, Philip; Le, Nhu D.; Lee, Eunjung; Lejbkowicz, Flavio; Lenz, Heinz-Josef; Leslie, Goska; Lessel, Davor; Lester, Jenny; Levine, Douglas A.; Li, Li; Li, Christopher I.; Lindblom, Annika; Lindor, Noralane M.; Liu, Geoffrey; Loupakis, Fotios; Lubinski, Jan; Maehle, Lovise; Maier, Christiane; Mannermaa, Arto; Le Marchand, Loic; Margolin, Sara; May, Taymaa; McGuffog, Lesley; Meindl, Alfons; Middha, Pooja; Miller, Austin; Milne, Roger L.; MacInnis, Robert J.; Modugno, Francesmary; Montagna, Marco; Moreno, Victor; Moysich, Kirsten B.; Mucci, Lorelei; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Neal, David E.; Ness, Andrew R.; Neuhausen, Susan L.; Nevanlinna, Heli; Newcomb, Polly A.; Newcomb, Lisa F.; Nielsen, Finn Cilius; Nikitina-Zake, Liene; Nordestgaard, Borge G.; Nussbaum, Robert L.; Offit, Kenneth; Olah, Edith; Al Olama, Ali Amin; Olopade, Olufunmilayo I.; Olshan, Andrew F.; Olsson, Hakan; Osorio, Ana; Pandha, Hardev; Park, Jong Y.; Pashayan, Nora; Parsons, Michael T.; Pejovic, Tanja; Penney, Kathryn L.; Peters, Wilbert H. M.; Phelan, Catherine M.; Phipps, Amanda I.; Plaseska-Karanfilska, Dijana; Pring, Miranda; Prokofyeva, Darya; Radice, Paolo; Stefansson, Kari; Ramus, Susan J.; Raskin, Leon; Rennert, Gad; Rennert, Hedy S.; van Rensburg, Elizabeth J.; Riggan, Marjorie J.; Risch, Harvey A.; Risch, Angela; Roobol, Monique J.; Rosenstein, Barry S.; Rossing, Mary Anne; De Ruyck, Kim; Saloustros, Emmanouil; Sandler, Dale P.; Sawyer, Elinor J.; Schabath, Matthew B.; Schleutker, Johanna; Schmidt, Marjanka K.; Setiawan, V. Wendy; Shen, Hongbing; Siegel, Erin M.; Sieh, Weiva; Singer, Christian F.; Slattery, Martha L.; Sorensen, Karina Dalsgaard; Southey, Melissa C.; Spurdle, Amanda B.; Stanford, Janet L.; Stevens, Victoria L.; Stintzing, Sebastian; Stone, Jennifer; Sundfeldt, Karin; Sutphen, Rebecca; Swerdlow, Anthony J.; Tajara, Eloiza H.; Tangen, Catherine M.; Tardon, Adonina; Taylor, Jack A.; Teare, M. Dawn; Teixeira, Manuel R.; Terry, Mary Beth; Terry, Kathryn L.; Thibodeau, Stephen N.; Thomassen, Mads; Bjorge, Line; Tischkowitz, Marc; Toland, Amanda E.; Torres, Diana; Townsend, Paul A.; Travis, Ruth C.; Tung, Nadine; Tworoger, Shelley S.; Ulrich, Cornelia M.; Usmani, Nawaid; Vachon, Celine M.; Van Nieuwenhuysen, Els; Vega, Ana; Aguado-Barrera, Miguel Elias; Wang, Qin; Webb, Penelope M.; Weinberg, Clarice R.; Weinstein, Stephanie; Weissler, Mark C.; Weitzel, Jeffrey N.; West, Catharine M. L.; White, Emily; Whittemore, Alice S.; Wichmann, H-Erich; Wiklund, Fredrik; Winqvist, Robert; Wolk, Alicja; Woll, Penella; Woods, Michael; Wu, Anna H.; Wu, Xifeng; Yannoukakos, Drakoulis; Zheng, Wei; Zienolddiny, Shanbeh; Ziogas, Argyrios; Zorn, Kristin K.; Lane, Jacqueline M.; Saxena, Richa; Thomas, Duncan; Hung, Rayjean J.; Diergaarde, Brenda; Mckay, James; Peters, Ulrike; Hsu, Li; Garcia-Closas, Montserrat; Eeles, Rosalind A.; Chenevix-Trench, Georgia; Brennan, Paul J.; Haiman, Christopher A.; Simard, Jacques; Easton, Douglas F.; Gruber, Stephen B.; Pharoah, Paul D. P.; Price, Alkes L.; Pasaniuc, Bogdan; Amos, Christopher I.; Kraft, Peter; Lindstrom, Sara (2019-01-25)
 
Avaa tiedosto
Lataukset: 

URL:
https://doi.org/10.1038/s41467-018-08054-4

Jiang, Xia
Finucane, Hilary K.
Schumacher, Fredrick R.
Schmit, Stephanie L.
Tyrer, Jonathan P.
Han, Younghun
Michailidou, Kyriaki
Lesseur, Corina
Kuchenbaecker, Karoline B.
Dennis, Joe
Conti, David V.
Casey, Graham
Gaudet, Mia M.
Huyghe, Jeroen R.
Albanes, Demetrius
Aldrich, Melinda C.
Andrew, Angeline S.
Andrulis, Irene L.
Anton-Culver, Hoda
Antoniou, Antonis C.
Antonenkova, Natalia N.
Arnold, Susanne M.
Aronson, Kristan J.
Arun, Banu K.
Bandera, Elisa V.
Barkardottir, Rosa B.
Barnes, Daniel R.
Batra, Jyotsna
Beckmann, Matthias W.
Benitez, Javier
Benlloch, Sara
Berchuck, Andrew
Berndt, Sonja I.
Bickeboeller, Heike
Bien, Stephanie A.
Blomqvist, Carl
Boccia, Stefania
Bogdanova, Natalia V.
Bojesen, Stig E.
Bolla, Manjeet K.
Brauch, Hiltrud
Brenner, Hermann
Brenton, James D.
Brook, Mark N.
Brunet, Joan
Brunnstrom, Hans
Buchanan, Daniel D.
Burwinkel, Barbara
Butzow, Ralf
Cadoni, Gabriella
Caldes, Trinidad
Caligo, Maria A.
Campbell, Ian
Campbell, Peter T.
Cancel-Tassin, Geraldine
Cannon-Albright, Lisa
Campa, Daniele
Caporaso, Neil
Carvalho, Andre L.
Chan, Andrew T.
Chang-Claude, Jenny
Chanock, Stephen J.
Chen, Chu
Christiani, David C.
Claes, Kathleen B. M.
Claessens, Frank
Clements, Judith
Collee, J. Margriet
Correa, Marcia Cruz
Couch, Fergus J.
Cox, Angela
Cunningham, Julie M.
Cybulski, Cezary
Czene, Kamila
Daly, Mary B.
defazio, Anna
Devilee, Peter
Diez, Orland
Gago-Dominguez, Manuela
Donovan, Jenny L.
Doerk, Thilo
Duell, Eric J.
Dunning, Alison M.
Dwek, Miriam
Eccles, Diana M.
Edlund, Christopher K.
Edwards, Digna R. Velez
Ellberg, Carolina
Evans, D. Gareth
Fasching, Peter A.
Ferris, Robert L.
Liloglou, Triantafillos
Figueiredo, Jane C.
Fletcher, Olivia
Fortner, Renee T.
Fostira, Florentia
Franceschi, Silvia
Friedman, Eitan
Gallinger, Steven J.
Ganz, Patricia A.
Garber, Judy
Garcia-Saenz, Jose A.
Gayther, Simon A.
Giles, Graham G.
Godwin, Andrew K.
Goldberg, Mark S.
Goldgar, David E.
Goode, Ellen L.
Goodman, Marc T.
Goodman, Gary
Grankvist, Kjell
Greene, Mark H.
Gronberg, Henrik
Gronwald, Jacek
Guenel, Pascal
Hakansson, Niclas
Hall, Per
Hamann, Ute
Hamdy, Freddie C.
Hamilton, Robert J.
Hampe, Jochen
Haugen, Aage
Heitz, Florian
Herrero, Rolando
Hillemanns, Peter
Hoffmeister, Michael
Hogdall, Estrid
Hong, Yun-Chul
Hopper, John L.
Houlston, Richard
Hulick, Peter J.
Hunter, David J.
Huntsman, David G.
Idos, Gregory
Imyanitov, Evgeny N.
Ingles, Sue Ann
Isaacs, Claudine
Jakubowska, Anna
James, Paul
Jenkins, Mark A.
Johansson, Mattias
Johansson, Mikael
John, Esther M.
Joshi, Amit D.
Kaneva, Radka
Karlan, Beth Y.
Kelemen, Linda E.
Kuhl, Tabea
Khaw, Kay-Tee
Khusnutdinova, Elza
Kibel, Adam S.
Kiemeney, Lambertus A.
Kim, Jeri
Kjaer, Susanne K.
Knight, Julia A.
Kogevinas, Manolis
Kote-Jarai, Zsofia
Koutros, Stella
Kristensen, Vessela N.
Kupryjanczyk, Jolanta
Lacko, Martin
Lam, Stephan
Lambrechts, Diether
Landi, Maria Teresa
Lazarus, Philip
Le, Nhu D.
Lee, Eunjung
Lejbkowicz, Flavio
Lenz, Heinz-Josef
Leslie, Goska
Lessel, Davor
Lester, Jenny
Levine, Douglas A.
Li, Li
Li, Christopher I.
Lindblom, Annika
Lindor, Noralane M.
Liu, Geoffrey
Loupakis, Fotios
Lubinski, Jan
Maehle, Lovise
Maier, Christiane
Mannermaa, Arto
Le Marchand, Loic
Margolin, Sara
May, Taymaa
McGuffog, Lesley
Meindl, Alfons
Middha, Pooja
Miller, Austin
Milne, Roger L.
MacInnis, Robert J.
Modugno, Francesmary
Montagna, Marco
Moreno, Victor
Moysich, Kirsten B.
Mucci, Lorelei
Muir, Kenneth
Mulligan, Anna Marie
Nathanson, Katherine L.
Neal, David E.
Ness, Andrew R.
Neuhausen, Susan L.
Nevanlinna, Heli
Newcomb, Polly A.
Newcomb, Lisa F.
Nielsen, Finn Cilius
Nikitina-Zake, Liene
Nordestgaard, Borge G.
Nussbaum, Robert L.
Offit, Kenneth
Olah, Edith
Al Olama, Ali Amin
Olopade, Olufunmilayo I.
Olshan, Andrew F.
Olsson, Hakan
Osorio, Ana
Pandha, Hardev
Park, Jong Y.
Pashayan, Nora
Parsons, Michael T.
Pejovic, Tanja
Penney, Kathryn L.
Peters, Wilbert H. M.
Phelan, Catherine M.
Phipps, Amanda I.
Plaseska-Karanfilska, Dijana
Pring, Miranda
Prokofyeva, Darya
Radice, Paolo
Stefansson, Kari
Ramus, Susan J.
Raskin, Leon
Rennert, Gad
Rennert, Hedy S.
van Rensburg, Elizabeth J.
Riggan, Marjorie J.
Risch, Harvey A.
Risch, Angela
Roobol, Monique J.
Rosenstein, Barry S.
Rossing, Mary Anne
De Ruyck, Kim
Saloustros, Emmanouil
Sandler, Dale P.
Sawyer, Elinor J.
Schabath, Matthew B.
Schleutker, Johanna
Schmidt, Marjanka K.
Setiawan, V. Wendy
Shen, Hongbing
Siegel, Erin M.
Sieh, Weiva
Singer, Christian F.
Slattery, Martha L.
Sorensen, Karina Dalsgaard
Southey, Melissa C.
Spurdle, Amanda B.
Stanford, Janet L.
Stevens, Victoria L.
Stintzing, Sebastian
Stone, Jennifer
Sundfeldt, Karin
Sutphen, Rebecca
Swerdlow, Anthony J.
Tajara, Eloiza H.
Tangen, Catherine M.
Tardon, Adonina
Taylor, Jack A.
Teare, M. Dawn
Teixeira, Manuel R.
Terry, Mary Beth
Terry, Kathryn L.
Thibodeau, Stephen N.
Thomassen, Mads
Bjorge, Line
Tischkowitz, Marc
Toland, Amanda E.
Torres, Diana
Townsend, Paul A.
Travis, Ruth C.
Tung, Nadine
Tworoger, Shelley S.
Ulrich, Cornelia M.
Usmani, Nawaid
Vachon, Celine M.
Van Nieuwenhuysen, Els
Vega, Ana
Aguado-Barrera, Miguel Elias
Wang, Qin
Webb, Penelope M.
Weinberg, Clarice R.
Weinstein, Stephanie
Weissler, Mark C.
Weitzel, Jeffrey N.
West, Catharine M. L.
White, Emily
Whittemore, Alice S.
Wichmann, H-Erich
Wiklund, Fredrik
Winqvist, Robert
Wolk, Alicja
Woll, Penella
Woods, Michael
Wu, Anna H.
Wu, Xifeng
Yannoukakos, Drakoulis
Zheng, Wei
Zienolddiny, Shanbeh
Ziogas, Argyrios
Zorn, Kristin K.
Lane, Jacqueline M.
Saxena, Richa
Thomas, Duncan
Hung, Rayjean J.
Diergaarde, Brenda
Mckay, James
Peters, Ulrike
Hsu, Li
Garcia-Closas, Montserrat
Eeles, Rosalind A.
Chenevix-Trench, Georgia
Brennan, Paul J.
Haiman, Christopher A.
Simard, Jacques
Easton, Douglas F.
Gruber, Stephen B.
Pharoah, Paul D. P.
Price, Alkes L.
Pasaniuc, Bogdan
Amos, Christopher I.
Kraft, Peter
Lindstrom, Sara
Springer Nature
25.01.2019

Jiang, X., Finucane, H.K., Schumacher, F.R. et al. Shared heritability and functional enrichment across six solid cancers. Nat Commun 10, 431 (2019). https://doi.org/10.1038/s41467-018-08054-4

https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
doi:https://doi.org/10.1038/s41467-018-08054-4
Näytä kaikki kuvailutiedot
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe202003117823
Tiivistelmä

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.

Kokoelmat
https://creativecommons.org/licenses/by/4.0/
Ellei muuten mainita, aineiston lisenssi on https://creativecommons.org/licenses/by/4.0/