Shared heritability and functional enrichment across six solid cancers

The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; Xia Jiang; Hilary K. Finucane; Fredrick R. Schumacher; Stephanie L. Schmit; Jonathan P. Tyrer; Younghun Han; Kyriaki Michailidou; Corina Lesseur; Karoline B. Kuchenbaecker; Joe Dennis; Jyotsna Batra

doi:10.1038/s41467-018-08054-4

Shared heritability and functional enrichment across six solid cancers

The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, Jyotsna Batra

Research output: Contribution to journal › Article › Research › peer-review

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
Pages (from-to)	1-23
Number of pages	23
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08054-4
Publication status	Published - 25 Jan 2019
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Shared heritability and functional enrichment across six solid cancersFinal published version, 3.74 MBLicence: CC BY

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The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., & Batra, J. (2019). Shared heritability and functional enrichment across six solid cancers. Nature Communications, 10(1), 1-23. Article 431. https://doi.org/10.1038/s41467-018-08054-4

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title = "Shared heritability and functional enrichment across six solid cancers",

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.",

author = "{The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium} and Xia Jiang and Finucane, {Hilary K.} and Schumacher, {Fredrick R.} and Schmit, {Stephanie L.} and Tyrer, {Jonathan P.} and Younghun Han and Kyriaki Michailidou and Corina Lesseur and Kuchenbaecker, {Karoline B.} and Joe Dennis and Conti, {David V.} and Graham Casey and Gaudet, {Mia M.} and Huyghe, {Jeroen R.} and Demetrius Albanes and Aldrich, {Melinda C.} and Andrew, {Angeline S.} and Andrulis, {Irene L.} and Hoda Anton-Culver 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 Jyotsna Batra and Beckmann, {Matthias W.} and Javier Benitez and Sara Benlloch and Andrew Berchuck and Berndt, {Sonja I.} and Heike Bickeb{\"o}ller and Bien, {Stephanie A.} and Carl Blomqvist and Stefania Boccia and Bogdanova, {Natalia V.} and Bojesen, {Stig E.} and Bolla, {Manjeet K.} and Hiltrud Brauch and Hermann Brenner and Brenton, {James D.} and Brook, {Mark N.} and Joan Brunet and Hans Brunnstr{\"o}m and Buchanan, {Daniel D.} and Barbara Burwinkel and Ralf Butzow and Gabriella Cadoni and Trinidad Cald{\'e}s and Caligo, {Maria A.} and Ian Campbell and Campbell, {Peter T.} and G{\'e}raldine Cancel-Tassin and Lisa Cannon-Albright and Daniele Campa and Neil Caporaso and Carvalho, {Andr{\'e} L.} and Chan, {Andrew T.} and Jenny Chang-Claude and Chanock, {Stephen J.} and Chu Chen and Christiani, {David C.} and Claes, {Kathleen B.M.} and Frank Claessens and Judith Clements and Coll{\'e}e, {J. Margriet} and Correa, {Marcia Cruz} and Couch, {Fergus J.} and Angela Cox and Cunningham, {Julie M.} and Cezary Cybulski and Kamila Czene and Daly, {Mary B.} and Anna deFazio and Peter Devilee and Orland Diez and Manuela Gago-Dominguez and Donovan, {Jenny L.} and Thilo D{\"o}rk and Duell, {Eric J.} and Dunning, {Alison M.} and Miriam Dwek and Eccles, {Diana M.} and Edlund, {Christopher K.} and Edwards, {Digna R.Velez} and Carolina Ellberg and Evans, {D. Gareth} and Fasching, {Peter A.} and Ferris, {Robert L.} and Triantafillos Liloglou and Figueiredo, {Jane C.} and Olivia Fletcher and Fortner, {Ren{\'e}e T.} and Florentia Fostira and Silvia Franceschi and Eitan Friedman and Gallinger, {Steven J.} and Ganz, {Patricia A.}",

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doi = "10.1038/s41467-018-08054-4",

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The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Jiang, X, Finucane, HK, Schumacher, FR, Schmit, SL, Tyrer, JP, Han, Y, Michailidou, K, Lesseur, C, Kuchenbaecker, KB, Dennis, J & Batra, J 2019, 'Shared heritability and functional enrichment across six solid cancers', Nature Communications, vol. 10, no. 1, 431, pp. 1-23. https://doi.org/10.1038/s41467-018-08054-4

Shared heritability and functional enrichment across six solid cancers. / The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; Jiang, Xia; Finucane, Hilary K. et al.
In: Nature Communications, Vol. 10, No. 1, 431, 25.01.2019, p. 1-23.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

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AU - The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

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.

AU - Huyghe, Jeroen R.

AU - Albanes, Demetrius

AU - Aldrich, Melinda C.

AU - Andrew, Angeline S.

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antoniou, Antonis C.

AU - Antonenkova, Natalia N.

AU - Arnold, Susanne M.

AU - Aronson, Kristan J.

AU - Arun, Banu K.

AU - Bandera, Elisa V.

AU - Barkardottir, Rosa B.

AU - Barnes, Daniel R.

AU - Batra, Jyotsna

AU - Beckmann, Matthias W.

AU - Benitez, Javier

AU - Benlloch, Sara

AU - Berchuck, Andrew

AU - Berndt, Sonja I.

AU - Bickeböller, Heike

AU - Bien, Stephanie A.

AU - Blomqvist, Carl

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AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Bolla, Manjeet K.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

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AU - Brook, Mark N.

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AU - Buchanan, Daniel D.

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AU - Cadoni, Gabriella

AU - Caldés, Trinidad

AU - Caligo, Maria A.

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AU - Campbell, Peter T.

AU - Cancel-Tassin, Géraldine

AU - Cannon-Albright, Lisa

AU - Campa, Daniele

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AU - Chang-Claude, Jenny

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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

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AU - Ferris, Robert L.

AU - Liloglou, Triantafillos

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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.

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DO - 10.1038/s41467-018-08054-4

M3 - Article

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SP - 1

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JO - Nature Communications

JF - Nature Communications

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M1 - 431

ER -

Shared heritability and functional enrichment across six solid cancers

Abstract

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Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4)

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Shared heritability and functional enrichment across six solid cancers

Abstract

UN SDGs

Access to Document

Other files and links

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Related Research Outputs

Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4)

Cite this