Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

Mark P. Purdue; Diptavo Dutta; Mitchell J. Machiela; Bryan R. Gorman; Timothy Winter; Dayne Okuhara; Sara Cleland; Aida Ferreiro-Iglesias; Paul Scheet; Aoxing Liu; Chao Wu; Samuel O. Antwi; James Larkin; Stênio C. Zequi; Maxine Sun; Keiko Hikino; Ali Hajiran; Keith A. Lawson; Flavio Cárcano; Odile Blanchet; Brian Shuch; Kenneth G. Nepple; Gaëlle Margue; Debasish Sundi; W. Ryan Diver; Maria A.A.K. Folgueira; Adrie van Bokhoven; Florencia Neffa; Kevin M. Brown; Jonathan N. Hofmann; Jongeun Rhee; Meredith Yeager; Nathan R. Cole; Belynda D. Hicks; Michelle R. Manning; Amy A. Hutchinson; Nathaniel Rothman; Wen Yi Huang; W. Marston Linehan; Adriana Lori; Matthieu Ferragu; Merzouka Zidane-Marinnes; Sérgio V. Serrano; Wesley J. Magnabosco; Ana Vilas; Ricardo Decia; Florencia Carusso; Laura S. Graham; Kyra Anderson; Mehmet A. Bilen; Cletus Arciero; Isabelle Pellegrin; Solène Ricard; Ghislaine Scelo; Rosamonde E. Banks; Naveen S. Vasudev; Naeem Soomro; Grant D. Stewart; Adebanji Adeyoju; Stephen Bromage; David Hrouda; Norma Gibbons; Poulam Patel; Mark Sullivan; Andrew Protheroe; Francesca I. Nugent; Michelle J. Fournier; Xiaoyu Zhang; Lisa J. Martin; Maria Komisarenko; Timothy Eisen; Sonia A. Cunningham; Denise C. Connolly; Robert G. Uzzo; David Zaridze; Anush Mukeria; Ivana Holcatova; Anna Hornakova; Lenka Foretova; Vladimir Janout; Dana Mates; Viorel Jinga; Stefan Rascu; Mirjana Mijuskovic; Slavisa Savic; Sasa Milosavljevic; Valérie Gaborieau; Behnoush Abedi-Ardekani; James McKay; Mattias Johansson; Larry Phouthavongsy; Lindsay Hayman; Jason Li; Ilinca Lungu; Stephania M. Bezerra; Aline G. Souza; Claudia T.G. Sares; Rodolfo B. Reis; Fabio P. Gallucci; Mauricio D. Cordeiro; Mark Pomerantz; Gwo Shu M. Lee; Matthew L. Freedman; Anhyo Jeong; Samantha E. Greenberg; Alejandro Sanchez; R. Houston Thompson; Vidit Sharma; David D. Thiel; Colleen T. Ball; Diego Abreu; Elaine T. Lam; William C. Nahas; Viraj A. Master; Alpa V. Patel; Jean Christophe Bernhard; Neal D. Freedman; Pierre Bigot; Rui M. Reis; Leandro M. Colli; Antonio Finelli; Brandon J. Manley; Chikashi Terao; Toni K. Choueiri; Dirce M. Carraro; Richard Houlston; Jeanette E. Eckel-Passow; Philip H. Abbosh; Andrea Ganna; Paul Brennan; Jian Gu; Stephen J. Chanock

doi:10.1038/s41588-024-01725-7

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

Mark P. Purdue
, Diptavo Dutta
, Mitchell J. Machiela
, Bryan R. Gorman
, Timothy Winter
, Dayne Okuhara
, Sara Cleland
, Aida Ferreiro-Iglesias
, Paul Scheet
, Aoxing Liu
, Chao Wu
, Samuel O. Antwi
, James Larkin
, Stênio C. Zequi
, Maxine Sun
, Keiko Hikino
, Ali Hajiran
, Keith A. Lawson
, Flavio Cárcano
, Odile Blanchet

Brian Shuch, Kenneth G. Nepple, Gaëlle Margue, Debasish Sundi, W. Ryan Diver, Maria A.A.K. Folgueira, Adrie van Bokhoven, Florencia Neffa, Kevin M. Brown, Jonathan N. Hofmann, Jongeun Rhee, Meredith Yeager, Nathan R. Cole, Belynda D. Hicks, Michelle R. Manning, Amy A. Hutchinson, Nathaniel Rothman, Wen Yi Huang, W. Marston Linehan, Adriana Lori, Matthieu Ferragu, Merzouka Zidane-Marinnes, Sérgio V. Serrano, Wesley J. Magnabosco, Ana Vilas, Ricardo Decia, Florencia Carusso, Laura S. Graham, Kyra Anderson, Mehmet A. Bilen, Cletus Arciero, Isabelle Pellegrin, Solène Ricard, Ghislaine Scelo, Rosamonde E. Banks, Naveen S. Vasudev, Naeem Soomro, Grant D. Stewart, Adebanji Adeyoju, Stephen Bromage, David Hrouda, Norma Gibbons, Poulam Patel, Mark Sullivan, Andrew Protheroe, Francesca I. Nugent, Michelle J. Fournier, Xiaoyu Zhang, Lisa J. Martin, Maria Komisarenko, Timothy Eisen, Sonia A. Cunningham, Denise C. Connolly, Robert G. Uzzo, David Zaridze, Anush Mukeria, Ivana Holcatova, Anna Hornakova, Lenka Foretova, Vladimir Janout, Dana Mates, Viorel Jinga, Stefan Rascu, Mirjana Mijuskovic, Slavisa Savic, Sasa Milosavljevic, Valérie Gaborieau, Behnoush Abedi-Ardekani, James McKay, Mattias Johansson, Larry Phouthavongsy, Lindsay Hayman, Jason Li, Ilinca Lungu, Stephania M. Bezerra, Aline G. Souza, Claudia T.G. Sares, Rodolfo B. Reis, Fabio P. Gallucci, Mauricio D. Cordeiro, Mark Pomerantz, Gwo Shu M. Lee, Matthew L. Freedman, Anhyo Jeong, Samantha E. Greenberg, Alejandro Sanchez, R. Houston Thompson, Vidit Sharma, David D. Thiel, Colleen T. Ball, Diego Abreu, Elaine T. Lam, William C. Nahas, Viraj A. Master, Alpa V. Patel, Jean Christophe Bernhard, Neal D. Freedman, Pierre Bigot, Rui M. Reis, Leandro M. Colli, Antonio Finelli, Brandon J. Manley, Chikashi Terao, Toni K. Choueiri, Dirce M. Carraro, Richard Houlston, Jeanette E. Eckel-Passow, Philip H. Abbosh, Andrea Ganna, Paul Brennan, Jian Gu, Stephen J. Chanock

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

43 被引用数 (Scopus)

抄録

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals (rs7629500) in the 3′ untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23–3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

本文言語	英語
ページ（範囲）	809-818
ページ数	10
ジャーナル	Nature Genetics
巻	56
号	5
DOI	https://doi.org/10.1038/s41588-024-01725-7
出版ステータス	出版済み - 05-2024
外部発表	はい

UN SDG

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All Science Journal Classification (ASJC) codes

遺伝学

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10.1038/s41588-024-01725-7

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Purdue, M. P., Dutta, D., Machiela, M. J., Gorman, B. R., Winter, T., Okuhara, D., Cleland, S., Ferreiro-Iglesias, A., Scheet, P., Liu, A., Wu, C., Antwi, S. O., Larkin, J., Zequi, S. C., Sun, M., Hikino, K., Hajiran, A., Lawson, K. A., Cárcano, F., ... Chanock, S. J. (2024). Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions. Nature Genetics, 56(5), 809-818. https://doi.org/10.1038/s41588-024-01725-7

@article{191a49e3629a4bef926cc2efc177f343,

title = "Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions",

abstract = "Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals (rs7629500) in the 3′ untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95\% confidence interval 2.23{\textendash}3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.",

author = "Purdue, \{Mark P.\} and Diptavo Dutta and Machiela, \{Mitchell J.\} and Gorman, \{Bryan R.\} and Timothy Winter and Dayne Okuhara and Sara Cleland and Aida Ferreiro-Iglesias and Paul Scheet and Aoxing Liu and Chao Wu and Antwi, \{Samuel O.\} and James Larkin and Zequi, \{St{\^e}nio C.\} and Maxine Sun and Keiko Hikino and Ali Hajiran and Lawson, \{Keith A.\} and Flavio C{\'a}rcano and Odile Blanchet and Brian Shuch and Nepple, \{Kenneth G.\} and Ga{\"e}lle Margue and Debasish Sundi and Diver, \{W. Ryan\} and Folgueira, \{Maria A.A.K.\} and \{van Bokhoven\}, Adrie and Florencia Neffa and Brown, \{Kevin M.\} and Hofmann, \{Jonathan N.\} and Jongeun Rhee and Meredith Yeager and Cole, \{Nathan R.\} and Hicks, \{Belynda D.\} and Manning, \{Michelle R.\} and Hutchinson, \{Amy A.\} and Nathaniel Rothman and Huang, \{Wen Yi\} and Linehan, \{W. Marston\} and Adriana Lori and Matthieu Ferragu and Merzouka Zidane-Marinnes and Serrano, \{S{\'e}rgio V.\} and Magnabosco, \{Wesley J.\} and Ana Vilas and Ricardo Decia and Florencia Carusso and Graham, \{Laura S.\} and Kyra Anderson and Bilen, \{Mehmet A.\} and Cletus Arciero and Isabelle Pellegrin and Sol{\`e}ne Ricard and Ghislaine Scelo and Banks, \{Rosamonde E.\} and Vasudev, \{Naveen S.\} and Naeem Soomro and Stewart, \{Grant D.\} and Adebanji Adeyoju and Stephen Bromage and David Hrouda and Norma Gibbons and Poulam Patel and Mark Sullivan and Andrew Protheroe and Nugent, \{Francesca I.\} and Fournier, \{Michelle J.\} and Xiaoyu Zhang and Martin, \{Lisa J.\} and Maria Komisarenko and Timothy Eisen and Cunningham, \{Sonia A.\} and Connolly, \{Denise C.\} and Uzzo, \{Robert G.\} and David Zaridze and Anush Mukeria and Ivana Holcatova and Anna Hornakova and Lenka Foretova and Vladimir Janout and Dana Mates and Viorel Jinga and Stefan Rascu and Mirjana Mijuskovic and Slavisa Savic and Sasa Milosavljevic and Val{\'e}rie Gaborieau and Behnoush Abedi-Ardekani and James McKay and Mattias Johansson and Larry Phouthavongsy and Lindsay Hayman and Jason Li and Ilinca Lungu and Bezerra, \{Stephania M.\} and Souza, \{Aline G.\} and Sares, \{Claudia T.G.\} and Reis, \{Rodolfo B.\} and Gallucci, \{Fabio P.\} and Cordeiro, \{Mauricio D.\} and Mark Pomerantz and Lee, \{Gwo Shu M.\} and Freedman, \{Matthew L.\} and Anhyo Jeong and Greenberg, \{Samantha E.\} and Alejandro Sanchez and Thompson, \{R. Houston\} and Vidit Sharma and Thiel, \{David D.\} and Ball, \{Colleen T.\} and Diego Abreu and Lam, \{Elaine T.\} and Nahas, \{William C.\} and Master, \{Viraj A.\} and Patel, \{Alpa V.\} and Bernhard, \{Jean Christophe\} and Freedman, \{Neal D.\} and Pierre Bigot and Reis, \{Rui M.\} and Colli, \{Leandro M.\} and Antonio Finelli and Manley, \{Brandon J.\} and Chikashi Terao and Choueiri, \{Toni K.\} and Carraro, \{Dirce M.\} and Richard Houlston and Eckel-Passow, \{Jeanette E.\} and Abbosh, \{Philip H.\} and Andrea Ganna and Paul Brennan and Jian Gu and Chanock, \{Stephen J.\}",

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.",

year = "2024",

month = may,

doi = "10.1038/s41588-024-01725-7",

language = "English",

volume = "56",

pages = "809--818",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

}

Purdue, MP, Dutta, D, Machiela, MJ, Gorman, BR, Winter, T, Okuhara, D, Cleland, S, Ferreiro-Iglesias, A, Scheet, P, Liu, A, Wu, C, Antwi, SO, Larkin, J, Zequi, SC, Sun, M, Hikino, K, Hajiran, A, Lawson, KA, Cárcano, F, Blanchet, O, Shuch, B, Nepple, KG, Margue, G, Sundi, D, Diver, WR, Folgueira, MAAK, van Bokhoven, A, Neffa, F, Brown, KM, Hofmann, JN, Rhee, J, Yeager, M, Cole, NR, Hicks, BD, Manning, MR, Hutchinson, AA, Rothman, N, Huang, WY, Linehan, WM, Lori, A, Ferragu, M, Zidane-Marinnes, M, Serrano, SV, Magnabosco, WJ, Vilas, A, Decia, R, Carusso, F, Graham, LS, Anderson, K, Bilen, MA, Arciero, C, Pellegrin, I, Ricard, S, Scelo, G, Banks, RE, Vasudev, NS, Soomro, N, Stewart, GD, Adeyoju, A, Bromage, S, Hrouda, D, Gibbons, N, Patel, P, Sullivan, M, Protheroe, A, Nugent, FI, Fournier, MJ, Zhang, X, Martin, LJ, Komisarenko, M, Eisen, T, Cunningham, SA, Connolly, DC, Uzzo, RG, Zaridze, D, Mukeria, A, Holcatova, I, Hornakova, A, Foretova, L, Janout, V, Mates, D, Jinga, V, Rascu, S, Mijuskovic, M, Savic, S, Milosavljevic, S, Gaborieau, V, Abedi-Ardekani, B, McKay, J, Johansson, M, Phouthavongsy, L, Hayman, L, Li, J, Lungu, I, Bezerra, SM, Souza, AG, Sares, CTG, Reis, RB, Gallucci, FP, Cordeiro, MD, Pomerantz, M, Lee, GSM, Freedman, ML, Jeong, A, Greenberg, SE, Sanchez, A, Thompson, RH, Sharma, V, Thiel, DD, Ball, CT, Abreu, D, Lam, ET, Nahas, WC, Master, VA, Patel, AV, Bernhard, JC, Freedman, ND, Bigot, P, Reis, RM, Colli, LM, Finelli, A, Manley, BJ, Terao, C, Choueiri, TK, Carraro, DM, Houlston, R, Eckel-Passow, JE, Abbosh, PH, Ganna, A, Brennan, P, Gu, J & Chanock, SJ 2024, 'Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions', Nature Genetics, vol. 56, no. 5, pp. 809-818. https://doi.org/10.1038/s41588-024-01725-7

TY - JOUR

T1 - Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

AU - Purdue, Mark P.

AU - Dutta, Diptavo

AU - Machiela, Mitchell J.

AU - Gorman, Bryan R.

AU - Winter, Timothy

AU - Okuhara, Dayne

AU - Cleland, Sara

AU - Ferreiro-Iglesias, Aida

AU - Scheet, Paul

AU - Liu, Aoxing

AU - Wu, Chao

AU - Antwi, Samuel O.

AU - Larkin, James

AU - Zequi, Stênio C.

AU - Sun, Maxine

AU - Hikino, Keiko

AU - Hajiran, Ali

AU - Lawson, Keith A.

AU - Cárcano, Flavio

AU - Blanchet, Odile

AU - Shuch, Brian

AU - Nepple, Kenneth G.

AU - Margue, Gaëlle

AU - Sundi, Debasish

AU - Diver, W. Ryan

AU - Folgueira, Maria A.A.K.

AU - van Bokhoven, Adrie

AU - Neffa, Florencia

AU - Brown, Kevin M.

AU - Hofmann, Jonathan N.

AU - Rhee, Jongeun

AU - Yeager, Meredith

AU - Cole, Nathan R.

AU - Hicks, Belynda D.

AU - Manning, Michelle R.

AU - Hutchinson, Amy A.

AU - Rothman, Nathaniel

AU - Huang, Wen Yi

AU - Linehan, W. Marston

AU - Lori, Adriana

AU - Ferragu, Matthieu

AU - Zidane-Marinnes, Merzouka

AU - Serrano, Sérgio V.

AU - Magnabosco, Wesley J.

AU - Vilas, Ana

AU - Decia, Ricardo

AU - Carusso, Florencia

AU - Graham, Laura S.

AU - Anderson, Kyra

AU - Bilen, Mehmet A.

AU - Arciero, Cletus

AU - Pellegrin, Isabelle

AU - Ricard, Solène

AU - Scelo, Ghislaine

AU - Banks, Rosamonde E.

AU - Vasudev, Naveen S.

AU - Soomro, Naeem

AU - Stewart, Grant D.

AU - Adeyoju, Adebanji

AU - Bromage, Stephen

AU - Hrouda, David

AU - Gibbons, Norma

AU - Patel, Poulam

AU - Sullivan, Mark

AU - Protheroe, Andrew

AU - Nugent, Francesca I.

AU - Fournier, Michelle J.

AU - Zhang, Xiaoyu

AU - Martin, Lisa J.

AU - Komisarenko, Maria

AU - Eisen, Timothy

AU - Cunningham, Sonia A.

AU - Connolly, Denise C.

AU - Uzzo, Robert G.

AU - Zaridze, David

AU - Mukeria, Anush

AU - Holcatova, Ivana

AU - Hornakova, Anna

AU - Foretova, Lenka

AU - Janout, Vladimir

AU - Mates, Dana

AU - Jinga, Viorel

AU - Rascu, Stefan

AU - Mijuskovic, Mirjana

AU - Savic, Slavisa

AU - Milosavljevic, Sasa

AU - Gaborieau, Valérie

AU - Abedi-Ardekani, Behnoush

AU - McKay, James

AU - Johansson, Mattias

AU - Phouthavongsy, Larry

AU - Hayman, Lindsay

AU - Li, Jason

AU - Lungu, Ilinca

AU - Bezerra, Stephania M.

AU - Souza, Aline G.

AU - Sares, Claudia T.G.

AU - Reis, Rodolfo B.

AU - Gallucci, Fabio P.

AU - Cordeiro, Mauricio D.

AU - Pomerantz, Mark

AU - Lee, Gwo Shu M.

AU - Freedman, Matthew L.

AU - Jeong, Anhyo

AU - Greenberg, Samantha E.

AU - Sanchez, Alejandro

AU - Thompson, R. Houston

AU - Sharma, Vidit

AU - Thiel, David D.

AU - Ball, Colleen T.

AU - Abreu, Diego

AU - Lam, Elaine T.

AU - Nahas, William C.

AU - Master, Viraj A.

AU - Patel, Alpa V.

AU - Bernhard, Jean Christophe

AU - Freedman, Neal D.

AU - Bigot, Pierre

AU - Reis, Rui M.

AU - Colli, Leandro M.

AU - Finelli, Antonio

AU - Manley, Brandon J.

AU - Terao, Chikashi

AU - Choueiri, Toni K.

AU - Carraro, Dirce M.

AU - Houlston, Richard

AU - Eckel-Passow, Jeanette E.

AU - Abbosh, Philip H.

AU - Ganna, Andrea

AU - Brennan, Paul

AU - Gu, Jian

AU - Chanock, Stephen J.

PY - 2024/5

Y1 - 2024/5

N2 - Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals (rs7629500) in the 3′ untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23–3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

AB - Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals (rs7629500) in the 3′ untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23–3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

UR - https://www.scopus.com/pages/publications/85191307064

UR - https://www.scopus.com/pages/publications/85191307064#tab=citedBy

U2 - 10.1038/s41588-024-01725-7

DO - 10.1038/s41588-024-01725-7

M3 - Article

C2 - 38671320

AN - SCOPUS:85191307064

SN - 1061-4036

VL - 56

SP - 809

EP - 818

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

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