Shared heritability and functional enrichment across six solid cancers

X. Jiang; H.K. Finucane; F.R. Schumacher; S.L. Schmit; J.P. Tyrer; Y.H. Han; K. Michailidou; C. Lesseur; K.B. Kuchenbaecker; J. Dennis; D.V. Conti; G. Casey; M.M. Gaudet; J.R. Huyghe; D. Albanes; M.C. Aldrich; A.S. Andrew; I.L. Andrulis; H. Anton-Culver; A.C. Antoniou; N.N. Antonenkova; S.M. Arnold; K.J. Aronson; B.K. Arun; E.V. Bandera; R.B. Barkardottir; D.R. Barnes; J. Batra; M.W. Beckmann; J. Benitez; S. Benlloch; A. Berchuck; S.I. Berndt; H. Bickeboller; S.A. Bien; C. Blomqvist; S. Boccia; N.V. Bogdanova; S.E. Bojesen; M.K. Bolla; H. Brauch; H. Brenner; J.D. Brenton; M.N. Brook; J. Brunet; H. Brunnstrom; D.D. Buchanan; B. Burwinkel; R. Butzow; G. Cadoni; Peter Kraft; Sara Lindstrom; Martin Lacko

doi:10.1038/s41467-018-08054-4

Shared heritability and functional enrichment across six solid cancers

X. Jiang^*, H.K. Finucane, F.R. Schumacher, S.L. Schmit, J.P. Tyrer, Y.H. Han, K. Michailidou, C. Lesseur, K.B. Kuchenbaecker, J. Dennis, D.V. Conti, G. Casey, M.M. Gaudet, J.R. Huyghe, D. Albanes, M.C. Aldrich, A.S. Andrew, I.L. Andrulis, H. Anton-Culver, A.C. AntoniouN.N. Antonenkova, S.M. Arnold, K.J. Aronson, B.K. Arun, E.V. Bandera, R.B. Barkardottir, D.R. Barnes, J. Batra, M.W. Beckmann, J. Benitez, S. Benlloch, A. Berchuck, S.I. Berndt, H. Bickeboller, S.A. Bien, C. Blomqvist, S. Boccia, N.V. Bogdanova, S.E. Bojesen, M.K. Bolla, H. Brauch, H. Brenner, J.D. Brenton, M.N. Brook, J. Brunet, H. Brunnstrom, D.D. Buchanan, B. Burwinkel, R. Butzow, G. Cadoni, Peter Kraft^*, Sara Lindstrom^*, Martin Lacko

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › 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 (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.

Original language	English
Article number	431
Number of pages	23
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-018-08054-4
Publication status	Published - 25 Jan 2019

Keywords

analyses identify
breast-cancer
cell-types
genetic architecture
genome-wide association
lung-cancer
mendelian randomization
partitioning heritability
risk-factors
susceptibility loci
RISK-FACTORS
PARTITIONING HERITABILITY
SUSCEPTIBILITY LOCI
GENETIC ARCHITECTURE
MENDELIAN RANDOMIZATION
BREAST-CANCER
LUNG-CANCER
ANALYSES IDENTIFY
CELL-TYPES
GENOME-WIDE ASSOCIATION

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1 Erratum / corrigendum / retractions

Publisher Correction: Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)
Author collaboration, 23 Sept 2019, In: Nature Communications. 10, 8 p., 4386.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

Open Access

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Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y. H., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., Conti, D. V., Casey, G., Gaudet, M. M., Huyghe, J. R., Albanes, D., Aldrich, M. C., Andrew, A. S., Andrulis, I. L., Anton-Culver, H., ... Lacko, M. (2019). Shared heritability and functional enrichment across six solid cancers. Nature Communications, 10, Article 431. https://doi.org/10.1038/s41467-018-08054-4

@article{5fb34aea52114b30b2819c8ee526a25e,

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 (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 = "analyses identify, breast-cancer, cell-types, genetic architecture, genome-wide association, lung-cancer, mendelian randomization, partitioning heritability, risk-factors, susceptibility loci, RISK-FACTORS, PARTITIONING HERITABILITY, SUSCEPTIBILITY LOCI, GENETIC ARCHITECTURE, MENDELIAN RANDOMIZATION, BREAST-CANCER, LUNG-CANCER, ANALYSES IDENTIFY, CELL-TYPES, GENOME-WIDE ASSOCIATION",

author = "X. Jiang and H.K. Finucane and F.R. Schumacher and S.L. Schmit and J.P. Tyrer and Y.H. Han and K. Michailidou and C. Lesseur and K.B. Kuchenbaecker and J. Dennis and D.V. Conti and G. Casey and M.M. Gaudet and J.R. Huyghe and D. Albanes and M.C. Aldrich and A.S. Andrew and I.L. Andrulis and H. Anton-Culver and A.C. Antoniou and N.N. Antonenkova and S.M. Arnold and K.J. Aronson and B.K. Arun and E.V. Bandera and R.B. Barkardottir and D.R. Barnes and J. Batra and M.W. Beckmann and J. Benitez and S. Benlloch and A. Berchuck and S.I. Berndt and H. Bickeboller and S.A. Bien and C. Blomqvist and S. Boccia and N.V. Bogdanova and S.E. Bojesen and M.K. Bolla and H. Brauch and H. Brenner and J.D. Brenton and M.N. Brook and J. Brunet and H. Brunnstrom and D.D. Buchanan and B. Burwinkel and R. Butzow and G. Cadoni and Peter Kraft and Sara Lindstrom and Martin Lacko",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

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

language = "English",

volume = "10",

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Jiang, X, Finucane, HK, Schumacher, FR, Schmit, SL, Tyrer, JP, Han, YH, 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, Bickeboller, H, Bien, SA, Blomqvist, C, Boccia, S, Bogdanova, NV, Bojesen, SE, Bolla, MK, Brauch, H, Brenner, H, Brenton, JD, Brook, MN, Brunet, J, Brunnstrom, H, Buchanan, DD, Burwinkel, B, Butzow, R, Cadoni, G, Kraft, P, Lindstrom, S & Lacko, M 2019, 'Shared heritability and functional enrichment across six solid cancers', Nature Communications, vol. 10, 431. https://doi.org/10.1038/s41467-018-08054-4

TY - JOUR

T1 - Shared heritability and functional enrichment across six solid cancers

AU - Jiang, X.

AU - Finucane, H.K.

AU - Schumacher, F.R.

AU - Schmit, S.L.

AU - Tyrer, J.P.

AU - Han, Y.H.

AU - Michailidou, K.

AU - Lesseur, C.

AU - Kuchenbaecker, K.B.

AU - Dennis, J.

AU - Conti, D.V.

AU - Casey, G.

AU - Gaudet, M.M.

AU - Huyghe, J.R.

AU - Albanes, D.

AU - Aldrich, M.C.

AU - Andrew, A.S.

AU - Andrulis, I.L.

AU - Anton-Culver, H.

AU - Antoniou, A.C.

AU - Antonenkova, N.N.

AU - Arnold, S.M.

AU - Aronson, K.J.

AU - Arun, B.K.

AU - Bandera, E.V.

AU - Barkardottir, R.B.

AU - Barnes, D.R.

AU - Batra, J.

AU - Beckmann, M.W.

AU - Benitez, J.

AU - Benlloch, S.

AU - Berchuck, A.

AU - Berndt, S.I.

AU - Bickeboller, H.

AU - Bien, S.A.

AU - Blomqvist, C.

AU - Boccia, S.

AU - Bogdanova, N.V.

AU - Bojesen, S.E.

AU - Bolla, M.K.

AU - Brauch, H.

AU - Brenner, H.

AU - Brenton, J.D.

AU - Brook, M.N.

AU - Brunet, J.

AU - Brunnstrom, H.

AU - Buchanan, D.D.

AU - Burwinkel, B.

AU - Butzow, R.

AU - Cadoni, G.

AU - Kraft, Peter

AU - Lindstrom, Sara

AU - Lacko, Martin

PY - 2019/1/25

Y1 - 2019/1/25

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 (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.

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 (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.

KW - analyses identify

KW - breast-cancer

KW - cell-types

KW - genetic architecture

KW - genome-wide association

KW - lung-cancer

KW - mendelian randomization

KW - partitioning heritability

KW - risk-factors

KW - susceptibility loci

KW - RISK-FACTORS

KW - PARTITIONING HERITABILITY

KW - SUSCEPTIBILITY LOCI

KW - GENETIC ARCHITECTURE

KW - MENDELIAN RANDOMIZATION

KW - BREAST-CANCER

KW - LUNG-CANCER

KW - ANALYSES IDENTIFY

KW - CELL-TYPES

KW - GENOME-WIDE ASSOCIATION

U2 - 10.1038/s41467-018-08054-4

DO - 10.1038/s41467-018-08054-4

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

M1 - 431

ER -

Shared heritability and functional enrichment across six solid cancers

Abstract

Keywords

Access to Document

Research output

Publisher Correction: Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)

Cite this