Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21

Quinn T. Ostrom; Ben Kinnersley; Margaret R. Wrensch; Jeanette E. Eckel-Passow; Georgina Armstrong; Terri Rice; Yanwen Chen; John K. Wiencke; Lucie S. McCoy; Helen M. Hansen; Christopher I. Amos; Jonine L. Bernstein; Elizabeth B. Claus; Dora Il'yasova; Christoffer Johansen; Daniel H. Lachance; Rose K. Lai; Ryan T. Merrell; Sara H. Olson; Siegal Sadetzki; Joellen M. Schildkraut; Sanjay Shete; Joshua B. Rubin; Justin D. Lathia; Michael E. Berens; Ulrika Andersson; Preetha Rajaraman; Stephen J. Chanock; Martha S. Linet; Zhaoming Wang; Meredith Yeager; Laura E. Beane Freeman; Stella Koutros; Demetrius Albanes; Kala Visvanathan; Victoria L. Stevens; Roger Henriksson; Dominique S. Michaud; Maria Feychting; Anders Ahlbom; Graham G. Giles; Roger Milne; Roberta McKean-Cowdin; Loic Le Marchand; Meir Stampfer; Avima M. Ruder; Tania Carreon; Göran Hallmans; Anne Zeleniuch-Jacquotte; J. Michael Gaziano; Howard D. Sesso; Mark P. Purdue; Emily White; Ulrike Peters; Julie Buring; Richard S. Houlston; Robert B. Jenkins; Beatrice Melin; Melissa L. Bondy; Jill S. Barnholtz-Sloan

doi:10.1038/s41598-018-24580-z

Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21

Quinn T. Ostrom, Ben Kinnersley, Margaret R. Wrensch, Jeanette E. Eckel-Passow, Georgina Armstrong, Terri Rice, Yanwen Chen, John K. Wiencke, Lucie S. McCoy, Helen M. Hansen, Christopher I. Amos, Jonine L. Bernstein, Elizabeth B. Claus, Dora Il'yasova, Christoffer Johansen, Daniel H. Lachance, Rose K. Lai, Ryan T. Merrell, Sara H. Olson, Siegal SadetzkiJoellen M. Schildkraut, Sanjay Shete, Joshua B. Rubin, Justin D. Lathia, Michael E. Berens, Ulrika Andersson, Preetha Rajaraman, Stephen J. Chanock, Martha S. Linet, Zhaoming Wang, Meredith Yeager, Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Kala Visvanathan, Victoria L. Stevens, Roger Henriksson, Dominique S. Michaud, Maria Feychting, Anders Ahlbom, Graham G. Giles, Roger Milne, Roberta McKean-Cowdin, Loic Le Marchand, Meir Stampfer, Avima M. Ruder, Tania Carreon, Göran Hallmans, Anne Zeleniuch-Jacquotte, J. Michael Gaziano, Howard D. Sesso, Mark P. Purdue, Emily White, Ulrike Peters, Julie Buring, Richard S. Houlston, Robert B. Jenkins, Beatrice Melin, Melissa L. Bondy, Jill S. Barnholtz-Sloan

Bloomberg School of Public Health

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Abstract

Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

Original language	English (US)
Article number	7352
Journal	Scientific reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-24580-z
State	Published - Dec 1 2018

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Ostrom, Q. T., Kinnersley, B., Wrensch, M. R., Eckel-Passow, J. E., Armstrong, G., Rice, T., Chen, Y., Wiencke, J. K., McCoy, L. S., Hansen, H. M., Amos, C. I., Bernstein, J. L., Claus, E. B., Il'yasova, D., Johansen, C., Lachance, D. H., Lai, R. K., Merrell, R. T., Olson, S. H., ... Barnholtz-Sloan, J. S. (2018). Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21. Scientific reports, 8(1), Article 7352. https://doi.org/10.1038/s41598-018-24580-z

Ostrom, QT, Kinnersley, B, Wrensch, MR, Eckel-Passow, JE, Armstrong, G, Rice, T, Chen, Y, Wiencke, JK, McCoy, LS, Hansen, HM, Amos, CI, Bernstein, JL, Claus, EB, Il'yasova, D, Johansen, C, Lachance, DH, Lai, RK, Merrell, RT, Olson, SH, Sadetzki, S, Schildkraut, JM, Shete, S, Rubin, JB, Lathia, JD, Berens, ME, Andersson, U, Rajaraman, P, Chanock, SJ, Linet, MS, Wang, Z, Yeager, M, Beane Freeman, LE, Koutros, S, Albanes, D, Visvanathan, K, Stevens, VL, Henriksson, R, Michaud, DS, Feychting, M, Ahlbom, A, Giles, GG, Milne, R, McKean-Cowdin, R, Le Marchand, L, Stampfer, M, Ruder, AM, Carreon, T, Hallmans, G, Zeleniuch-Jacquotte, A, Gaziano, JM, Sesso, HD, Purdue, MP, White, E, Peters, U, Buring, J, Houlston, RS, Jenkins, RB, Melin, B, Bondy, ML & Barnholtz-Sloan, JS 2018, 'Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21', Scientific reports, vol. 8, no. 1, 7352. https://doi.org/10.1038/s41598-018-24580-z

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title = "Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21",

abstract = "Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.",

author = "Ostrom, {Quinn T.} and Ben Kinnersley and Wrensch, {Margaret R.} and Eckel-Passow, {Jeanette E.} and Georgina Armstrong and Terri Rice and Yanwen Chen and Wiencke, {John K.} and McCoy, {Lucie S.} and Hansen, {Helen M.} and Amos, {Christopher I.} and Bernstein, {Jonine L.} and Claus, {Elizabeth B.} and Dora Il'yasova and Christoffer Johansen and Lachance, {Daniel H.} and Lai, {Rose K.} and Merrell, {Ryan T.} and Olson, {Sara H.} and Siegal Sadetzki and Schildkraut, {Joellen M.} and Sanjay Shete and Rubin, {Joshua B.} and Lathia, {Justin D.} and Berens, {Michael E.} and Ulrika Andersson and Preetha Rajaraman and Chanock, {Stephen J.} and Linet, {Martha S.} and Zhaoming Wang and Meredith Yeager and {Beane Freeman}, {Laura E.} and Stella Koutros and Demetrius Albanes and Kala Visvanathan and Stevens, {Victoria L.} and Roger Henriksson and Michaud, {Dominique S.} and Maria Feychting and Anders Ahlbom and Giles, {Graham G.} and Roger Milne and Roberta McKean-Cowdin and {Le Marchand}, Loic and Meir Stampfer and Ruder, {Avima M.} and Tania Carreon and G{\"o}ran Hallmans and Anne Zeleniuch-Jacquotte and Gaziano, {J. Michael} and Sesso, {Howard D.} and Purdue, {Mark P.} and Emily White and Ulrike Peters and Julie Buring and Houlston, {Richard S.} and Jenkins, {Robert B.} and Beatrice Melin and Bondy, {Melissa L.} and Barnholtz-Sloan, {Jill S.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-24580-z",

language = "English (US)",

volume = "8",

journal = "Scientific reports",

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TY - JOUR

T1 - Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21

AU - Ostrom, Quinn T.

AU - Kinnersley, Ben

AU - Wrensch, Margaret R.

AU - Eckel-Passow, Jeanette E.

AU - Armstrong, Georgina

AU - Rice, Terri

AU - Chen, Yanwen

AU - Wiencke, John K.

AU - McCoy, Lucie S.

AU - Hansen, Helen M.

AU - Amos, Christopher I.

AU - Bernstein, Jonine L.

AU - Claus, Elizabeth B.

AU - Il'yasova, Dora

AU - Johansen, Christoffer

AU - Lachance, Daniel H.

AU - Lai, Rose K.

AU - Merrell, Ryan T.

AU - Olson, Sara H.

AU - Sadetzki, Siegal

AU - Schildkraut, Joellen M.

AU - Shete, Sanjay

AU - Rubin, Joshua B.

AU - Lathia, Justin D.

AU - Berens, Michael E.

AU - Andersson, Ulrika

AU - Rajaraman, Preetha

AU - Chanock, Stephen J.

AU - Linet, Martha S.

AU - Wang, Zhaoming

AU - Yeager, Meredith

AU - Beane Freeman, Laura E.

AU - Koutros, Stella

AU - Albanes, Demetrius

AU - Visvanathan, Kala

AU - Stevens, Victoria L.

AU - Henriksson, Roger

AU - Michaud, Dominique S.

AU - Feychting, Maria

AU - Ahlbom, Anders

AU - Giles, Graham G.

AU - Milne, Roger

AU - McKean-Cowdin, Roberta

AU - Le Marchand, Loic

AU - Stampfer, Meir

AU - Ruder, Avima M.

AU - Carreon, Tania

AU - Hallmans, Göran

AU - Zeleniuch-Jacquotte, Anne

AU - Gaziano, J. Michael

AU - Sesso, Howard D.

AU - Purdue, Mark P.

AU - White, Emily

AU - Peters, Ulrike

AU - Buring, Julie

AU - Houlston, Richard S.

AU - Jenkins, Robert B.

AU - Melin, Beatrice

AU - Bondy, Melissa L.

AU - Barnholtz-Sloan, Jill S.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

AB - Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

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U2 - 10.1038/s41598-018-24580-z

DO - 10.1038/s41598-018-24580-z

M3 - Article

C2 - 29743610

AN - SCOPUS:85046904855

SN - 2045-2322

VL - 8

JO - Scientific reports

JF - Scientific reports

IS - 1

M1 - 7352

ER -

Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21

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