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

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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 languageEnglish (US)
Article number7352
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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ASJC Scopus subject areas

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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), [7352]. https://doi.org/10.1038/s41598-018-24580-z