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.

性别特异性神经胶质瘤全基因组关联研究确定了女性 3p21.31 的新风险位点 ，并在 8q24.21 发现风险的性别差异。

• 影响指数: 4.996
• 发表时间: 05 2018 9
• 来源期刊: Sci Rep
• DOI: 10.1038/s41598-018-24580-z
• PMID: 29743610
• 文章类型: Journal Article
• 中科院分区: Q1
• 方向: 综合性期刊
• 作者列表: 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, ,Houlston RS,Jenkins RB,Melin B,Bondy ML,Barnholtz-Sloan JS

Mesh: Adult; Alleles; Brain Neoplasms / pathology; Case-Control Studies; Chromosomes, Human, Pair 3 / genetics; Chromosomes, Human, Pair 7 / genetics; Chromosomes, Human, Pair 8 / genetics; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Glioma / genetics metabolism pathology; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide / genetics; Risk Factors; Sex Factors

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.

摘要

男性神经胶质瘤的发病率大约高出50%。先前的分析已经检查了与女性性激素相关的暴露作为这些肿瘤的潜在保护因素，结果不一致。先前的神经胶质瘤全基因组关联研究（GWAS）尚未按性别分层。在所有神经胶质瘤的常染色体SNP和性染色体变异中评估了潜在的性别特异性遗传效应，GBM和非GBM患者使用来自四个先前神经胶质瘤GWAS的数据。使用性别分层逻辑回归模型分析数据集，并使用荟萃分析进行组合。有4,831例男性病例，5,216名男性对照，3206例女性病例和5470例女性对照。仅在男性中，rs11979158（7p11.2）检测到显着关联。女性rs55705857（8q24.21）的关联性强于男性。仅在女性中，3p21.31上的一个大区域被确定为具有显着相关性。确定的风险变异效果差异不能完全解释所观察到的性别神经胶质瘤发病率差异。