A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer.
A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer.
复制标题
DOI：
10.1016/j.ijrobp.2012.08.003
复制
发表时间：
2013-01-01
影响因子：
7
通讯作者：
Rosenstein, Barry S.
中科院分区：
文献类型：
--
作者：
Kerns, Sarah L.;Stock, Richard;Stone, Nelson;Buckstein, Michael;Shao, Yongzhao;Campbell, Christopher;Rath, Lynda;De Ruysscher, Dirk;Lammering, Guido;Hixson, Rosetta;Cesaretti, Jamie;Terk, Mitchell;Ostrer, Harry;Rosenstein, Barry S.
研究前列腺癌放疗患者中与勃起功能障碍相关的单核苷酸多态性（snp）。进行了两阶段全基因组关联研究（GWAS）。患者随机分为I期发现组（132例，103例对照）和II期重复组（128例，102例对照）。使用Affymetrix 6.0全基因组阵列对发现队列进行基因分型。使用Illumina iSelect自定义SNP阵列，从发现队列中选择940个排名最高的SNP在复制队列中进行基因分型。在发现队列中发现并在复制队列中验证的12个snp与放疗后ED的发展相关（Fisher组合p值2.1×10−5至6.2×10−4）。值得注意的是，这12个snp位于或靠近与勃起功能或其他正常细胞功能（粘附和信号）有关的基因，而不是DNA损伤修复。在包含非遗传风险因素的多变量模型中，这些snp的优势比在合并队列中从1.6到5.6不等。个体拥有的SNP风险等位基因的累积数量与ED状态之间存在显著的关系（Sommers ' D p值= 1.7×10−29）。累积SNP得分增加1个等位基因，发生ED的几率增加2.2倍（p值= 2.1×10−19）。累积SNP评分模型预测放疗计划阶段发生ED的敏感性为84%，特异性为75%。该GWAS鉴定了一组与放疗后ED发展相关的snp。这些候选遗传预测因子需要在独立队列中进行更明确的验证。
To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiotherapy. A two-stage genome-wide association study (GWAS) was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays. The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays. 12 SNPs identified in the discovery cohort and validated in the replication cohort were associated with development of ED following radiotherapy (Fisher combined p-values 2.1×10−5 to 6.2×10−4). Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and signaling) rather than DNA damage repair. In a multivariable model including non-genetic risk factors, the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status (Sommers’ D p-value = 1.7×10−29). A one-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 (p-value = 2.1×10−19). The cumulative SNP score model had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiotherapy planning stage. This GWAS identified a set of SNPs that are associated with development of ED following radiotherapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.
登录
查看更多内容
影响因子：
45.3
作者：
Talcott, JA;Manola, J;D'Amico, AV
通讯作者：
D'Amico, AV
影响因子：
4.8
作者：
Witte, S;Villalba, M;Altman, A
通讯作者：
Altman, A
影响因子：
1.9
作者：
Zagar, Timothy M.;Stock, Richard G.;Stone, Nelson N.
通讯作者：
Stone, Nelson N.
影响因子：
2.1
作者：
Rosenstein BS
通讯作者：
Rosenstein BS
影响因子：
64.8
作者：
Gibbs, RA;Belmont, JW;Tanaka, T
通讯作者：
Tanaka, T