GENETIC EPIDEMIOLOGY OF SARCOIDOSIS IN AFRICAN AMERICANS

非裔美国人结节病的遗传流行病学

• 批准号: 7420622
• 负责人: MICHAEL C IANNUZZI
• 金额: $ 0.74万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420622
• 关键词: chromosomes; epidemiology; genes; genetics; genome; sarcoidosis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology. Hereditary susceptibility to sarcoidosis is suggested by reports of familial clustering and a higher prevalence in certain ethnic groups, particularly African-Americans. Candidate genes for the granulomatous inflammatory disorders Blau syndrome and Crohn's disease have been localized to the centrometric region of chromosome 16. We found no evidence of linkage in this general region, and could exclude from it a dominant gene with relative risk at least 5, or a recessive gene with relative risk at least 3, causing sarcoidosis. A multicenter study to perform a whole genome scan in the search for susceptibility genes has been completed, as has fine mapping of six candidate regions identified in the genome scan. In the total 559 sib pairs that were enrolled, genetic analyses revealed incorrectly specified relationships that required reclassification or removal from the analysis dataset of 10.4% of reported full and 1.4% of reported half sib pairs. The final study sample comprised 415 full and 104 half sib pairs with complete data. This inclused 338 ASPs. Within sib pairs, affection status was not associated with sex. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak t D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。结节病是一种病因不明的多系统肉芽肿性炎症性疾病。家族聚集性报告表明结节病具有遗传易感性，并且在某些种族群体（尤其是非裔美国人）中患病率较高。肉芽肿性炎症性疾病布劳综合征和克罗恩病的候选基因已定位于 16 号染色体的中心区。我们在这个一般区域中没有发现连锁的证据，并且可以从中排除相对风险至少为 5 的显性基因，或者相对风险至少为 3 的隐性基因，导致结节病。一项进行全基因组扫描以寻找易感基因的多中心研究已经完成，基因组扫描中确定的六个候选区域的精细绘图也已完成。在总共登记的 559 对同胞中，遗传分析揭示了错误指定的关系，需要重新分类或从分析数据集中删除 10.4% 报告的完整同胞对和 1.4% 报告的半同胞对。最终研究样本包括 415 个全同胞对和 104 个半同胞对，具有完整的数据。其中包括 338 个 ASP。在同胞对中，情感状态与性别无关。使用 Haseman-Elston 回归技术，在染色体 1p22、2p25、5p15-13、5q11、5q35、9q34、11p15 和 20q13 上鉴定出 P 值小于 0.05 的连锁峰，其中最突出的峰 t D5S2500 在染色体 5q11 上（P =0.0005）。我们发现与之前报道的德国人群基因组扫描在染色体 1p 和 9q 上的连锁一致。根据我们在研究人群中发现的多个暗示性关联区域，很可能不止一种基因影响非裔美国人的结节病易感性。