A Genome-Wide Association Study of Non-Hodgkin Lymphoma

非霍奇金淋巴瘤的全基因组关联研究

• 批准号: 7479594
• 负责人: Christine F. Skibola
• 金额: $ 52.96万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-14 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479594
• 关键词: Accounting; Address; Alleles; Area; Bioinformatics; Biology; Candidate Disease Gene; Case-Control Studies; Cessation of life; Complex; DNA; Data; Depth; Developed Countries; Disease; Environmental Risk Factor; Epidemiologic Studies; Etiology; Family; Gene Frequency; Gene Targeting; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Research; Genome; Genotype; Goals; HLA Antigens; Haplotypes; Incidence; Individual; Investigation; Knowledge; Linkage Disequilibrium; Lymphoma; Lymphomagenesis; Maps; Minor; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Numbers; Oligonucleotide Microarrays; Participant; Pathogenesis; Pathway interactions; Play; Population; Population Study; Predisposition; Prevention; Public Health; Rate; Research Design; Research Personnel; Risk; Role; Sampling; San Francisco; Screening procedure; Signal Transduction; Single Nucleotide Polymorphism; Structure; Susceptibility Gene; Testing; Translating; Treatment Protocols; Validation; base; case control; cohort; cost; density; gene environment interaction; genetic association; genetic epidemiology; genome wide association study; interest; novel; programs; treatment program

DESCRIPTION (provided by applicant): Incidence rates of non-Hodgkin lymphoma (NHL) have increased dramatically in the U.S. and other industrialized countries over the past 40 years, though reasons for this rise in rates are largely unexplained. In 2005, it has been estimated that NHL will account for 56,390 newly diagnosed cases and 19,200 associated deaths. Family and population-based studies provide evidence that genetic susceptibility plays a role in lymphomagenesis. However, the contribution of common genetic alleles and gene-environment interactions needs further investigation. Using Perlegen high-density oligonucleotide arrays, genome-wide genotyping on pooled DNA will be conducted to screen for NHL susceptibility markers. 267,000 haplotype tagging single nucleotide polymorphisms (SNPs) will be evaluated that span the genome on DNA pools from 1,000 NHL cases and 1,000 controls in a large population-based case-control study in the San Francisco Bay Area (recruitment of 2,000 cases and 2,000 controls to be completed in Spring 2006). Over 1,400 cases and 1,400 controls already have been ascertained with extensive epidemiological information collected from all study participants. Once target genes are identified by pooled genotyping, the association of these loci with NHL risk will be verified and further investigated by individual genotyping. An additional 7,000 SNPs will be individually genotyped in the human leukocyte antigen (HLA) region to investigate the involvement of HLA loci in the pathogenesis of NHL. Positive findings will be replicated in a second set of 1,000 NHL cases and 1,000 controls. Fine mapping genotyping will be performed on confirmed genes of interest. To add an additional replication step, another approximately 400 NHL cases and 800 controls from a previous NHL study (based in the San Francisco Bay Area) will be genotyped. This study, which constitutes one of the largest case-control NHL genetic epidemiology studies conducted to date, will broaden our current understanding of important mechanistic pathways involved in lymphomagenesis. Furthermore, these results may be translated to NHL screening, prevention or treatment regimens. The data generated from this study will provide a framework for further investigation within the NHL consortium, InterLymph. Results will later be combined with that from other InterLymph case-control studies in pooled analyses.

描述（由申请人提供）：在过去的40年中，非霍奇金淋巴瘤（NHL）的发病率在美国和其他工业化国家的发病率显着增加，尽管这种率上升的原因在很大程度上无法解释。 2005年，据估计，NHL将占56,390例新诊断的病例和19,200例相关死亡。基于家庭和人群的研究提供了证据，表明遗传易感性在淋巴作用中起作用。但是，常见遗传等位基因和基因环境相互作用的贡献需要进一步研究。使用Perlegen高密度寡核苷酸阵列，将在汇总DNA上进行全基因组基因分型，以筛选NHL易感性标记。将评估267,000个单倍型标记单核苷酸多态性（SNP）（SNP），这些核苷酸多态性（SNP）跨越了来自1,000个NHL病例的DNA池上的基因组和在旧金山湾地区的大型基于人口的病例对照研究中（招募2,000例和2,000例对照，并在2006年春季招募2,000例对照）。已经确定了超过1,400例病例和1,400例对照，并从所有研究参与者那里收集了广泛的流行病学信息。一旦通过合并的基因分型鉴定了靶基因，这些基因座与NHL风险的关联将得到验证，并通过单个基因分型进一步研究。在人类白细胞抗原（HLA）区域中，将单独进行7,000个SNP，以研究HLA基因座在NHL的发病机理中的参与。积极的发现将在第二组NHL病例和1,000个对照组中复制。精细的映射基因分型将对确认的感兴趣基因进行。为了添加额外的复制步骤，将对先前的NHL研究（基于旧金山湾地区）的大约400例NHL病例和800个对照。这项研究构成了迄今为止进行的最大病例对照NHL遗传流行病学研究之一，它将扩大我们当前对涉及淋巴作用的重要机械途径的理解。此外，这些结果可以转化为NHL筛查，预防或治疗方案。这项研究产生的数据将为NHL财团内的Interlymph提供进一步研究的框架。稍后，结果将与其他Interlymph病例对照研究中的结果结合在一起。