Shared heritability and functional enrichment across six solid cancers

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, 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. AntoniouNatalia 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, Silvia Franceschi, Fotios Loupakis, Marco Montagna, Paolo Radice

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer (r g = 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 languageEnglish
Article number431
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

Fingerprint

cancer
Nucleic Acid Regulatory Sequences
Tumors
Neoplasms
Genes
Statistics
Tissue
breast
Head and Neck Neoplasms
Breast Neoplasms
Ovarian Neoplasms
lungs
Lung Neoplasms
Genome-Wide Association Study
Metabolic Diseases
etiology
Psychiatry
Colorectal Neoplasms
Prostatic Neoplasms
ovaries

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., ... Radice, P. (2019). Shared heritability and functional enrichment across six solid cancers. Nature Communications, 10(1), [431]. https://doi.org/10.1038/s41467-018-08054-4

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.; Bickeböller, 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; Brunnström, Hans; Franceschi, Silvia; Loupakis, Fotios; Montagna, Marco; Radice, Paolo.

In: Nature Communications, Vol. 10, No. 1, 431, 01.12.2019.

Research output: Contribution to journalArticle

Jiang, X, Finucane, HK, Schumacher, FR, Schmit, SL, Tyrer, JP, Han, Y, Michailidou, K, Lesseur, C, Kuchenbaecker, KB, Dennis, J, Conti, DV, Casey, G, Gaudet, MM, Huyghe, JR, Albanes, D, Aldrich, MC, Andrew, AS, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Antonenkova, NN, Arnold, SM, Aronson, KJ, Arun, BK, Bandera, EV, Barkardottir, RB, Barnes, DR, Batra, J, Beckmann, MW, Benitez, J, Benlloch, S, Berchuck, A, Berndt, SI, Bickeböller, H, Bien, SA, Blomqvist, C, Boccia, S, Bogdanova, NV, Bojesen, SE, Bolla, MK, Brauch, H, Brenner, H, Brenton, JD, Brook, MN, Brunet, J, Brunnström, H, Franceschi, S, Loupakis, F, Montagna, M & Radice, P 2019, 'Shared heritability and functional enrichment across six solid cancers', Nature Communications, vol. 10, no. 1, 431. https://doi.org/10.1038/s41467-018-08054-4
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 Dec 1;10(1). 431. 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. ; Bickeböller, 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 ; Brunnström, Hans ; Franceschi, Silvia ; Loupakis, Fotios ; Montagna, Marco ; Radice, Paolo. / Shared heritability and functional enrichment across six solid cancers. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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