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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 (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 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.
Keywords
GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY LOCI, BREAST-CANCER, RISK-FACTORS, LUNG-CANCER, PARTITIONING HERITABILITY, MENDELIAN RANDOMIZATION, GENETIC ARCHITECTURE, ANALYSES IDENTIFY, CELL-TYPES

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MLA
Jiang, Xia et al. “Shared Heritability and Functional Enrichment Across Six Solid Cancers.” NATURE COMMUNICATIONS 10 (2019): n. pag. Print.
APA
Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., et al. (2019). Shared heritability and functional enrichment across six solid cancers. NATURE COMMUNICATIONS, 10.
Chicago author-date
Jiang, Xia, Hilary K Finucane, Fredrick R Schumacher, Stephanie L Schmit, Jonathan P Tyrer, Younghun Han, Kyriaki Michailidou, et al. 2019. “Shared Heritability and Functional Enrichment Across Six Solid Cancers.” Nature Communications 10.
Chicago author-date (all authors)
Jiang, Xia, Hilary K Finucane, Fredrick R Schumacher, Stephanie L Schmit, Jonathan P Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B Kuchenbaecker, Joe Dennis, David V Conti, Graham Casey, Mia M Gaudet, Jeroen R Huyghe, Demetrius Albanes, Melinda C Aldrich, Angeline S Andrew, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Natalia N Antonenkova, Susanne M Arnold, Kristan J Aronson, Banu K Arun, Elisa V Bandera, Rosa B Barkardottir, Daniel R Barnes, Jyotsna Batra, Matthias W Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I Berndt, Heike Bickeböller, Stephanie A Bien, Carl Blomqvist, Stefania Boccia, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Hiltrud Brauch, Hermann Brenner, James D Brenton, Mark N Brook, Joan Brunet, Hans Brunnström, Daniel D Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A Caligo, Ian Campbell, Peter T Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L Carvalho, Andrew T Chan, Jenny Chang-Claude, Stephen J Chanock, Chu Chen, David C Christiani, Kathleen Claes, Frank Claessens, Judith Clements, J Margriet Collée, Marcia Cruz Correa, Fergus J Couch, Angela Cox, Julie M Cunningham, Cezary Cybulski, Kamila Czene, Mary B Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L Donovan, Thilo Dörk, Eric J Duell, Alison M Dunning, Miriam Dwek, Diana M Eccles, Christopher K Edlund, Digna R Velez Edwards, Carolina Ellberg, D Gareth Evans, Peter A Fasching, Robert L Ferris, Triantafillos Liloglou, Jane C Figueiredo, Olivia Fletcher, Renée T Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J Gallinger, Patricia A Ganz, Judy Garber, José A García-Sáenz, Simon A Gayther, Graham G Giles, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Ellen L Goode, Marc T Goodman, Gary Goodman, Kjell Grankvist, Mark H Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C Hamdy, Robert J Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L Hopper, Richard Houlston, Peter J Hulick, David J Hunter, David G Huntsman, Gregory Idos, Evgeny N Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A Jenkins, Mattias Johansson, Mikael Johansson, Esther M John, Amit D Joshi, Radka Kaneva, Beth Y Karlan, Linda E Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S Kibel, Lambertus A Kiemeney, Jeri Kim, Susanne K Kjaer, Julia A Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A Levine, Li Li, Christopher I Li, Annika Lindblom, Noralane M Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L Milne, Robert J MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L Nathanson, David E Neal, Andrew R Ness, Susan L Neuhausen, Heli Nevanlinna, Polly A Newcomb, Lisa F Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G Nordestgaard, Robert L Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I Olopade, Andrew F Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y Park, Nora Pashayan, Michael T Parsons, Tanja Pejovic, Kathryn L Penney, Wilbert HM Peters, Catherine M Phelan, Amanda I Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J van Rensburg, Marjorie J Riggan, Harvey A Risch, Angela Risch, Monique J Roobol, Barry S Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P Sandler, Elinor J Sawyer, Matthew B Schabath, Johanna Schleutker, Marjanka K. Schmidt, V Wendy Setiawan, Hongbing Shen, Erin M Siegel, Weiva Sieh, Christian F Singer, Martha L Slattery, Karina Dalsgaard Sorensen, Melissa C Southey, Amanda B Spurdle, Janet L Stanford, Victoria L Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J Swerdlow, Eloiza H Tajara, Catherine M Tangen, Adonina Tardon, Jack A Taylor, M Dawn Teare, Manuel R Teixeira, Mary Beth Terry, Kathryn L Terry, Stephen N Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E Toland, Diana Torres, Paul A Townsend, Ruth C Travis, Nadine Tung, Shelley S Tworoger, Cornelia M Ulrich, Nawaid Usmani, Celine M Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M Webb, Clarice R Weinberg, Stephanie Weinstein, Mark C Weissler, Jeffrey N Weitzel, Catharine ML West, Emily White, Alice S Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K Zorn, Jacqueline M Lane, Richa Saxena, Duncan Thomas, Rayjean J Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A Eeles, Georgia Chenevix-Trench, Paul J Brennan, Christopher A. Haiman, Jacques Simard, Douglas F Easton, Stephen B Gruber, Paul DP Pharoah, Alkes L Price, Bogdan Pasaniuc, Christopher I Amos, Peter Kraft, and Sara Lindström. 2019. “Shared Heritability and Functional Enrichment Across Six Solid Cancers.” Nature Communications 10.
Vancouver
1.
Jiang X, Finucane HK, Schumacher FR, Schmit SL, Tyrer JP, Han Y, et al. Shared heritability and functional enrichment across six solid cancers. NATURE COMMUNICATIONS. 2019;10.
IEEE
[1]
X. Jiang et al., “Shared heritability and functional enrichment across six solid cancers,” NATURE COMMUNICATIONS, vol. 10, 2019.
@article{8598980,
  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 (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 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.},
  articleno    = {431},
  author       = {Jiang, Xia and Finucane, Hilary K and Schumacher, Fredrick R and Schmit, Stephanie L and Tyrer, Jonathan P and Han, Younghun and Michailidou, Kyriaki and Lesseur, Corina and Kuchenbaecker, Karoline B and Dennis, Joe and Conti, David V and Casey, Graham and Gaudet, Mia M and Huyghe, Jeroen R and Albanes, Demetrius and Aldrich, Melinda C and Andrew, Angeline S and Andrulis, Irene L and Anton-Culver, Hoda and Antoniou, Antonis C and Antonenkova, Natalia N and Arnold, Susanne M and Aronson, Kristan J and Arun, Banu K and Bandera, Elisa V and Barkardottir, Rosa B and Barnes, Daniel R and Batra, Jyotsna and Beckmann, Matthias W and Benitez, Javier and Benlloch, Sara and Berchuck, Andrew and Berndt, Sonja I and Bickeböller, Heike and Bien, Stephanie A and Blomqvist, Carl and Boccia, Stefania and Bogdanova, Natalia V and Bojesen, Stig E and Bolla, Manjeet K and Brauch, Hiltrud and Brenner, Hermann and Brenton, James D and Brook, Mark N and Brunet, Joan and Brunnström, Hans and Buchanan, Daniel D and Burwinkel, Barbara and Butzow, Ralf and Cadoni, Gabriella and Caldés, Trinidad and Caligo, Maria A and Campbell, Ian and Campbell, Peter T and Cancel-Tassin, Géraldine and Cannon-Albright, Lisa and Campa, Daniele and Caporaso, Neil and Carvalho, André L and Chan, Andrew T and Chang-Claude, Jenny and Chanock, Stephen J and Chen, Chu and Christiani, David C and Claes, Kathleen and Claessens, Frank and Clements, Judith and Collée, J Margriet and Correa, Marcia Cruz and Couch, Fergus J and Cox, Angela and Cunningham, Julie M and Cybulski, Cezary and Czene, Kamila and Daly, Mary B and deFazio, Anna and Devilee, Peter and Diez, Orland and Gago-Dominguez, Manuela and Donovan, Jenny L and Dörk, Thilo and Duell, Eric J and Dunning, Alison M and Dwek, Miriam and Eccles, Diana M and Edlund, Christopher K and Edwards, Digna R Velez and Ellberg, Carolina and Evans, D Gareth and Fasching, Peter A and Ferris, Robert L and Liloglou, Triantafillos and Figueiredo, Jane C and Fletcher, Olivia and Fortner, Renée T and Fostira, Florentia and Franceschi, Silvia and Friedman, Eitan and Gallinger, Steven J and Ganz, Patricia A and Garber, Judy and García-Sáenz, José A and Gayther, Simon A and Giles, Graham G and Godwin, Andrew K and Goldberg, Mark S and Goldgar, David E and Goode, Ellen L and Goodman, Marc T and Goodman, Gary and Grankvist, Kjell and Greene, Mark H and Gronberg, Henrik and Gronwald, Jacek and Guénel, Pascal and Håkansson, Niclas and Hall, Per and Hamann, Ute and Hamdy, Freddie C and Hamilton, Robert J and Hampe, Jochen and Haugen, Aage and Heitz, Florian and Herrero, Rolando and Hillemanns, Peter and Hoffmeister, Michael and Høgdall, Estrid and Hong, Yun-Chul and Hopper, John L and Houlston, Richard and Hulick, Peter J and Hunter, David J and Huntsman, David G and Idos, Gregory and Imyanitov, Evgeny N and Ingles, Sue Ann and Isaacs, Claudine and Jakubowska, Anna and James, Paul and Jenkins, Mark A and Johansson, Mattias and Johansson, Mikael and John, Esther M and Joshi, Amit D and Kaneva, Radka and Karlan, Beth Y and Kelemen, Linda E and Kühl, Tabea and Khaw, Kay-Tee and Khusnutdinova, Elza and Kibel, Adam S and Kiemeney, Lambertus A and Kim, Jeri and Kjaer, Susanne K and Knight, Julia A and Kogevinas, Manolis and Kote-Jarai, Zsofia and Koutros, Stella and Kristensen, Vessela N and Kupryjanczyk, Jolanta and Lacko, Martin and Lam, Stephan and Lambrechts, Diether and Landi, Maria Teresa and Lazarus, Philip and Le, Nhu D and Lee, Eunjung and Lejbkowicz, Flavio and Lenz, Heinz-Josef and Leslie, Goska and Lessel, Davor and Lester, Jenny and Levine, Douglas A and Li, Li and Li, Christopher I and Lindblom, Annika and Lindor, Noralane M and Liu, Geoffrey and Loupakis, Fotios and Lubiński, Jan and Maehle, Lovise and Maier, Christiane and Mannermaa, Arto and Le Marchand, Loic and Margolin, Sara and May, Taymaa and McGuffog, Lesley and Meindl, Alfons and Middha, Pooja and Miller, Austin and Milne, Roger L and MacInnis, Robert J and Modugno, Francesmary and Montagna, Marco and Moreno, Victor and Moysich, Kirsten B and Mucci, Lorelei and Muir, Kenneth and Mulligan, Anna Marie and Nathanson, Katherine L and Neal, David E and Ness, Andrew R and Neuhausen, Susan L and Nevanlinna, Heli and Newcomb, Polly A and Newcomb, Lisa F and Nielsen, Finn Cilius and Nikitina-Zake, Liene and Nordestgaard, Børge G and Nussbaum, Robert L and Offit, Kenneth and Olah, Edith and Olama, Ali Amin Al and Olopade, Olufunmilayo I and Olshan, Andrew F and Olsson, Håkan and Osorio, Ana and Pandha, Hardev and Park, Jong Y and Pashayan, Nora and Parsons, Michael T and Pejovic, Tanja and Penney, Kathryn L and Peters, Wilbert HM and Phelan, Catherine M and Phipps, Amanda I and Plaseska-Karanfilska, Dijana and Pring, Miranda and Prokofyeva, Darya and Radice, Paolo and Stefansson, Kari and Ramus, Susan J and Raskin, Leon and Rennert, Gad and Rennert, Hedy S. and van Rensburg, Elizabeth J and Riggan, Marjorie J and Risch, Harvey A and Risch, Angela and Roobol, Monique J and Rosenstein, Barry S and Rossing, Mary Anne and De Ruyck, Kim and Saloustros, Emmanouil and Sandler, Dale P and Sawyer, Elinor J and Schabath, Matthew B and Schleutker, Johanna and Schmidt, Marjanka K. and Setiawan, V Wendy and Shen, Hongbing and Siegel, Erin M and Sieh, Weiva and Singer, Christian F and Slattery, Martha L and Sorensen, Karina Dalsgaard and Southey, Melissa C and Spurdle, Amanda B and Stanford, Janet L and Stevens, Victoria L and Stintzing, Sebastian and Stone, Jennifer and Sundfeldt, Karin and Sutphen, Rebecca and Swerdlow, Anthony J and Tajara, Eloiza H and Tangen, Catherine M and Tardon, Adonina and Taylor, Jack A and Teare, M Dawn and Teixeira, Manuel R and Terry, Mary Beth and Terry, Kathryn L and Thibodeau, Stephen N and Thomassen, Mads and Bjørge, Line and Tischkowitz, Marc and Toland, Amanda E and Torres, Diana and Townsend, Paul A and Travis, Ruth C and Tung, Nadine and Tworoger, Shelley S and Ulrich, Cornelia M and Usmani, Nawaid and Vachon, Celine M and Van Nieuwenhuysen, Els and Vega, Ana and Aguado-Barrera, Miguel Elías and Wang, Qin and Webb, Penelope M and Weinberg, Clarice R and Weinstein, Stephanie and Weissler, Mark C and Weitzel, Jeffrey N and West, Catharine ML and White, Emily and Whittemore, Alice S and Wichmann, H-Erich and Wiklund, Fredrik and Winqvist, Robert and Wolk, Alicja and Woll, Penella and Woods, Michael and Wu, Anna H and Wu, Xifeng and Yannoukakos, Drakoulis and Zheng, Wei and Zienolddiny, Shanbeh and Ziogas, Argyrios and Zorn, Kristin K and Lane, Jacqueline M and Saxena, Richa and Thomas, Duncan and Hung, Rayjean J and Diergaarde, Brenda and McKay, James and Peters, Ulrike and Hsu, Li and García-Closas, Montserrat and Eeles, Rosalind A and Chenevix-Trench, Georgia and Brennan, Paul J and Haiman, Christopher A. and Simard, Jacques and Easton, Douglas F and Gruber, Stephen B and Pharoah, Paul DP and Price, Alkes L and Pasaniuc, Bogdan and Amos, Christopher I and Kraft, Peter and Lindström, Sara},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {GENOME-WIDE ASSOCIATION,SUSCEPTIBILITY LOCI,BREAST-CANCER,RISK-FACTORS,LUNG-CANCER,PARTITIONING HERITABILITY,MENDELIAN RANDOMIZATION,GENETIC ARCHITECTURE,ANALYSES IDENTIFY,CELL-TYPES},
  language     = {eng},
  pages        = {23},
  title        = {Shared heritability and functional enrichment across six solid cancers},
  url          = {http://dx.doi.org/10.1038/s41467-018-08054-4},
  volume       = {10},
  year         = {2019},
}

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