Sex specific associations in genome wide association analysis of renal cell carcinoma

Ruhina S. Laskar; David C. Muller; Peng Li; Mitchell J. Machiela; Yuanqing Ye; Valerie Gaborieau; Matthieu Foll; Jonathan N. Hofmann; Leandro Colli; Joshua N. Sampson; Zhaoming Wang; Delphine Bacq-Daian; Anne Boland; Behnoush Abedi-Ardekani; Geoffroy Durand; Florence Le Calvez-Kelm; Nivonirina Robinot; Helene Blanche; Egor Prokhortchouk; Konstantin G. Skryabin; Laurie Burdett; Meredith Yeager; Sanja Radojevic-Skodric; Slavisa Savic; Lenka Foretova; Ivana Holcatova; Vladimir Janout; Dana Mates; Stefan Rascu; Anush Mukeria; David Zaridze; Vladimir Bencko; Cezary Cybulski; Eleonora Fabianova; Viorel Jinga; Jolanta Lissowska; Jan Lubinski; Marie Navratilova; Peter Rudnai; Beata Świątkowska; Simone Benhamou; Geraldine Cancel-Tassin; Olivier Cussenot; Antonia Trichopoulou; Elio Riboli; Kim Overvad; Salvatore Panico; Borje Ljungberg; Raviprakash T. Sitaram; Graham G. Giles; Roger L. Milne; Gianluca Severi; Fiona Bruinsma; Tony Fletcher; Kvetoslava Koppova; Susanna C. Larsson; Alicja Wolk; Rosamonde E. Banks; Peter J. Selby; Douglas F. Easton; Paul Pharoah; Gabriella Andreotti; Laura E. Beane Freeman; Stella Koutros; Demetrius Albanes; Satu Männistö; Stephanie Weinstein; Peter E. Clark; Todd L. Edwards; Loren Lipworth; Hallie Carol; Matthew L. Freedman; Mark M. Pomerantz; Eunyoung Cho; Peter Kraft; Mark A. Preston; Kathryn M. Wilson; J. Michael Gaziano; Howard D. Sesso; Amanda Black; Neal D. Freedman; Wen Yi Huang; John G. Anema; Richard J. Kahnoski; Brian R. Lane; Sabrina L. Noyes; David Petillo; Bin Tean Teh; Ulrike Peters; Emily White; Garnet L. Anderson; Lisa Johnson; Juhua Luo; Wong Ho Chow; Lee E. Moore; Toni K. Choueiri; Christopher Wood; Mattias Johansson; James D. McKay; Kevin M. Brown; Nathaniel Rothman; Mark G. Lathrop; Jean Francois Deleuze; Xifeng Wu; Paul Brennan; Stephen J. Chanock; Mark P. Purdue; Ghislaine Scelo

doi:10.1038/s41431-019-0455-9

Sex specific associations in genome wide association analysis of renal cell carcinoma

Ruhina S. Laskar, David C. Muller, Peng Li, Mitchell J. Machiela, Yuanqing Ye, Valerie Gaborieau, Matthieu Foll, Jonathan N. Hofmann, Leandro Colli, Joshua N. Sampson, Zhaoming Wang, Delphine Bacq-Daian, Anne Boland, Behnoush Abedi-Ardekani, Geoffroy Durand, Florence Le Calvez-Kelm, Nivonirina Robinot, Helene Blanche, Egor Prokhortchouk, Konstantin G. SkryabinLaurie Burdett, Meredith Yeager, Sanja Radojevic-Skodric, Slavisa Savic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Stefan Rascu, Anush Mukeria, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Beata Świątkowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, Antonia Trichopoulou, Elio Riboli, Kim Overvad, Salvatore Panico, Borje Ljungberg, Raviprakash T. Sitaram, Graham G. Giles, Roger L. Milne, Gianluca Severi, Fiona Bruinsma, Tony Fletcher, Kvetoslava Koppova, Susanna C. Larsson, Alicja Wolk, Rosamonde E. Banks, Peter J. Selby, Douglas F. Easton, Paul Pharoah, Gabriella Andreotti, Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Männistö, Stephanie Weinstein, Peter E. Clark, Todd L. Edwards, Loren Lipworth, Hallie Carol, Matthew L. Freedman, Mark M. Pomerantz, Eunyoung Cho, Peter Kraft, Mark A. Preston, Kathryn M. Wilson, J. Michael Gaziano, Howard D. Sesso, Amanda Black, Neal D. Freedman, Wen Yi Huang, John G. Anema, Richard J. Kahnoski, Brian R. Lane, Sabrina L. Noyes, David Petillo, Bin Tean Teh, Ulrike Peters, Emily White, Garnet L. Anderson, Lisa Johnson, Juhua Luo, Wong Ho Chow, Lee E. Moore, Toni K. Choueiri, Christopher Wood, Mattias Johansson, James D. McKay, Kevin M. Brown, Nathaniel Rothman, Mark G. Lathrop, Jean Francois Deleuze, Xifeng Wu, Paul Brennan, Stephen J. Chanock, Mark P. Purdue, Ghislaine Scelo

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

25 Scopus citations

Abstract

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (OR_male) = 0.83 [95% CI = 0.78-0.89], P_male = 1.71 × 10⁻⁸ compared with female odds ratio (OR_female) = 0.98 [95% CI = 0.90–1.07], P_female = 0.68) and 12q23.3 (intergenic, OR_male = 0.75 [95% CI = 0.68-0.83], P_male = 1.59 × 10⁻⁸ compared with OR_female = 0.93 [95% CI = 0.82–1.06], P_female = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

Original language	English (US)
Pages (from-to)	1589-1598
Number of pages	10
Journal	European Journal of Human Genetics
Volume	27
Issue number	10
DOIs	https://doi.org/10.1038/s41431-019-0455-9
State	Published - Oct 1 2019

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1038/s41431-019-0455-9

Cite this

Laskar, R. S., Muller, D. C., Li, P., Machiela, M. J., Ye, Y., Gaborieau, V., Foll, M., Hofmann, J. N., Colli, L., Sampson, J. N., Wang, Z., Bacq-Daian, D., Boland, A., Abedi-Ardekani, B., Durand, G., Le Calvez-Kelm, F., Robinot, N., Blanche, H., Prokhortchouk, E., ... Scelo, G. (2019). Sex specific associations in genome wide association analysis of renal cell carcinoma. European Journal of Human Genetics, 27(10), 1589-1598. https://doi.org/10.1038/s41431-019-0455-9

Laskar, RS, Muller, DC, Li, P, Machiela, MJ, Ye, Y, Gaborieau, V, Foll, M, Hofmann, JN, Colli, L, Sampson, JN, Wang, Z, Bacq-Daian, D, Boland, A, Abedi-Ardekani, B, Durand, G, Le Calvez-Kelm, F, Robinot, N, Blanche, H, Prokhortchouk, E, Skryabin, KG, Burdett, L, Yeager, M, Radojevic-Skodric, S, Savic, S, Foretova, L, Holcatova, I, Janout, V, Mates, D, Rascu, S, Mukeria, A, Zaridze, D, Bencko, V, Cybulski, C, Fabianova, E, Jinga, V, Lissowska, J, Lubinski, J, Navratilova, M, Rudnai, P, Świątkowska, B, Benhamou, S, Cancel-Tassin, G, Cussenot, O, Trichopoulou, A, Riboli, E, Overvad, K, Panico, S, Ljungberg, B, Sitaram, RT, Giles, GG, Milne, RL, Severi, G, Bruinsma, F, Fletcher, T, Koppova, K, Larsson, SC, Wolk, A, Banks, RE, Selby, PJ, Easton, DF, Pharoah, P, Andreotti, G, Beane Freeman, LE, Koutros, S, Albanes, D, Männistö, S, Weinstein, S, Clark, PE, Edwards, TL, Lipworth, L, Carol, H, Freedman, ML, Pomerantz, MM, Cho, E, Kraft, P, Preston, MA, Wilson, KM, Michael Gaziano, J, Sesso, HD, Black, A, Freedman, ND, Huang, WY, Anema, JG, Kahnoski, RJ, Lane, BR, Noyes, SL, Petillo, D, Teh, BT, Peters, U, White, E, Anderson, GL, Johnson, L, Luo, J, Chow, WH, Moore, LE, Choueiri, TK, Wood, C, Johansson, M, McKay, JD, Brown, KM, Rothman, N, Lathrop, MG, Deleuze, JF, Wu, X, Brennan, P, Chanock, SJ, Purdue, MP & Scelo, G 2019, 'Sex specific associations in genome wide association analysis of renal cell carcinoma', European Journal of Human Genetics, vol. 27, no. 10, pp. 1589-1598. https://doi.org/10.1038/s41431-019-0455-9

@article{7b846e7981874ff5887b9df9ec239f37,

title = "Sex specific associations in genome wide association analysis of renal cell carcinoma",

abstract = "Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10−8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90–1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10−8 compared with ORfemale = 0.93 [95% CI = 0.82–1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.",

author = "Laskar, {Ruhina S.} and Muller, {David C.} and Peng Li and Machiela, {Mitchell J.} and Yuanqing Ye and Valerie Gaborieau and Matthieu Foll and Hofmann, {Jonathan N.} and Leandro Colli and Sampson, {Joshua N.} and Zhaoming Wang and Delphine Bacq-Daian and Anne Boland and Behnoush Abedi-Ardekani and Geoffroy Durand and {Le Calvez-Kelm}, Florence and Nivonirina Robinot and Helene Blanche and Egor Prokhortchouk and Skryabin, {Konstantin G.} and Laurie Burdett and Meredith Yeager and Sanja Radojevic-Skodric and Slavisa Savic and Lenka Foretova and Ivana Holcatova and Vladimir Janout and Dana Mates and Stefan Rascu and Anush Mukeria and David Zaridze and Vladimir Bencko and Cezary Cybulski and Eleonora Fabianova and Viorel Jinga and Jolanta Lissowska and Jan Lubinski and Marie Navratilova and Peter Rudnai and Beata {\'S}wi{\c a}tkowska and Simone Benhamou and Geraldine Cancel-Tassin and Olivier Cussenot and Antonia Trichopoulou and Elio Riboli and Kim Overvad and Salvatore Panico and Borje Ljungberg and Sitaram, {Raviprakash T.} and Giles, {Graham G.} and Milne, {Roger L.} and Gianluca Severi and Fiona Bruinsma and Tony Fletcher and Kvetoslava Koppova and Larsson, {Susanna C.} and Alicja Wolk and Banks, {Rosamonde E.} and Selby, {Peter J.} and Easton, {Douglas F.} and Paul Pharoah and Gabriella Andreotti and {Beane Freeman}, {Laura E.} and Stella Koutros and Demetrius Albanes and Satu M{\"a}nnist{\"o} and Stephanie Weinstein and Clark, {Peter E.} and Edwards, {Todd L.} and Loren Lipworth and Hallie Carol and Freedman, {Matthew L.} and Pomerantz, {Mark M.} and Eunyoung Cho and Peter Kraft and Preston, {Mark A.} and Wilson, {Kathryn M.} and {Michael Gaziano}, J. and Sesso, {Howard D.} and Amanda Black and Freedman, {Neal D.} and Huang, {Wen Yi} and Anema, {John G.} and Kahnoski, {Richard J.} and Lane, {Brian R.} and Noyes, {Sabrina L.} and David Petillo and Teh, {Bin Tean} and Ulrike Peters and Emily White and Anderson, {Garnet L.} and Lisa Johnson and Juhua Luo and Chow, {Wong Ho} and Moore, {Lee E.} and Choueiri, {Toni K.} and Christopher Wood and Mattias Johansson and McKay, {James D.} and Brown, {Kevin M.} and Nathaniel Rothman and Lathrop, {Mark G.} and Deleuze, {Jean Francois} and Xifeng Wu and Paul Brennan and Chanock, {Stephen J.} and Purdue, {Mark P.} and Ghislaine Scelo",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to European Society of Human Genetics.",

year = "2019",

month = oct,

day = "1",

doi = "10.1038/s41431-019-0455-9",

language = "English (US)",

volume = "27",

pages = "1589--1598",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Nature Publishing Group",

number = "10",

}

TY - JOUR

T1 - Sex specific associations in genome wide association analysis of renal cell carcinoma

AU - Laskar, Ruhina S.

AU - Muller, David C.

AU - Li, Peng

AU - Machiela, Mitchell J.

AU - Ye, Yuanqing

AU - Gaborieau, Valerie

AU - Foll, Matthieu

AU - Hofmann, Jonathan N.

AU - Colli, Leandro

AU - Sampson, Joshua N.

AU - Wang, Zhaoming

AU - Bacq-Daian, Delphine

AU - Boland, Anne

AU - Abedi-Ardekani, Behnoush

AU - Durand, Geoffroy

AU - Le Calvez-Kelm, Florence

AU - Robinot, Nivonirina

AU - Blanche, Helene

AU - Prokhortchouk, Egor

AU - Skryabin, Konstantin G.

AU - Burdett, Laurie

AU - Yeager, Meredith

AU - Radojevic-Skodric, Sanja

AU - Savic, Slavisa

AU - Foretova, Lenka

AU - Holcatova, Ivana

AU - Janout, Vladimir

AU - Mates, Dana

AU - Rascu, Stefan

AU - Mukeria, Anush

AU - Zaridze, David

AU - Bencko, Vladimir

AU - Cybulski, Cezary

AU - Fabianova, Eleonora

AU - Jinga, Viorel

AU - Lissowska, Jolanta

AU - Lubinski, Jan

AU - Navratilova, Marie

AU - Rudnai, Peter

AU - Świątkowska, Beata

AU - Benhamou, Simone

AU - Cancel-Tassin, Geraldine

AU - Cussenot, Olivier

AU - Trichopoulou, Antonia

AU - Riboli, Elio

AU - Overvad, Kim

AU - Panico, Salvatore

AU - Ljungberg, Borje

AU - Sitaram, Raviprakash T.

AU - Giles, Graham G.

AU - Milne, Roger L.

AU - Severi, Gianluca

AU - Bruinsma, Fiona

AU - Fletcher, Tony

AU - Koppova, Kvetoslava

AU - Larsson, Susanna C.

AU - Wolk, Alicja

AU - Banks, Rosamonde E.

AU - Selby, Peter J.

AU - Easton, Douglas F.

AU - Pharoah, Paul

AU - Andreotti, Gabriella

AU - Beane Freeman, Laura E.

AU - Koutros, Stella

AU - Albanes, Demetrius

AU - Männistö, Satu

AU - Weinstein, Stephanie

AU - Clark, Peter E.

AU - Edwards, Todd L.

AU - Lipworth, Loren

AU - Carol, Hallie

AU - Freedman, Matthew L.

AU - Pomerantz, Mark M.

AU - Cho, Eunyoung

AU - Kraft, Peter

AU - Preston, Mark A.

AU - Wilson, Kathryn M.

AU - Michael Gaziano, J.

AU - Sesso, Howard D.

AU - Black, Amanda

AU - Freedman, Neal D.

AU - Huang, Wen Yi

AU - Anema, John G.

AU - Kahnoski, Richard J.

AU - Lane, Brian R.

AU - Noyes, Sabrina L.

AU - Petillo, David

AU - Teh, Bin Tean

AU - Peters, Ulrike

AU - White, Emily

AU - Anderson, Garnet L.

AU - Johnson, Lisa

AU - Luo, Juhua

AU - Chow, Wong Ho

AU - Moore, Lee E.

AU - Choueiri, Toni K.

AU - Wood, Christopher

AU - Johansson, Mattias

AU - McKay, James D.

AU - Brown, Kevin M.

AU - Rothman, Nathaniel

AU - Lathrop, Mark G.

AU - Deleuze, Jean Francois

AU - Wu, Xifeng

AU - Brennan, Paul

AU - Chanock, Stephen J.

AU - Purdue, Mark P.

AU - Scelo, Ghislaine

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10−8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90–1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10−8 compared with ORfemale = 0.93 [95% CI = 0.82–1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

AB - Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10−8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90–1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10−8 compared with ORfemale = 0.93 [95% CI = 0.82–1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

UR - http://www.scopus.com/inward/record.url?scp=85068111474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068111474&partnerID=8YFLogxK

U2 - 10.1038/s41431-019-0455-9

DO - 10.1038/s41431-019-0455-9

M3 - Article

C2 - 31231134

AN - SCOPUS:85068111474

SN - 1018-4813

VL - 27

SP - 1589

EP - 1598

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 10

ER -

Sex specific associations in genome wide association analysis of renal cell carcinoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this