GENETIC EPIDEMIOLOGY OF SARCOIDOSIS IN AFRICAN AMERICANS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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。结节病的遗传易感性是由家族聚集性报告和某些种族群体，特别是非洲裔美国人较高的患病率提出的。肉芽肿性炎症性疾病Blau综合征和克罗恩病的候选基因已经定位于16号染色体的着丝区。我们没有发现在这个一般区域有关联的证据，可以排除一个相对危险度至少为5的显性基因，或一个相对危险度至少为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，同时在基因组扫描中确定了六个候选区域的精细定位。在纳入的559对同胞兄弟姐妹中，遗传分析显示10.4%的报告的全同胞兄弟姐妹和1.4%的报告的半同胞兄弟姐妹的关系指定不正确，需要从分析数据集中重新分类或删除。最终的研究样本包括415对全兄妹和104对半兄妹，数据完整。其中包括338个asp。在兄弟姐妹中，情感状态与性别无关。利用Haseman-Elston回归技术，在1p22、2525、5p15-13、5q11、5q35、9q34、11p15和20q13染色体上发现了P值小于0.05的连锁峰，其中5q11染色体上的D5S2500峰最为显著（P=0.0005）。我们发现与先前报道的德国人群染色体1p和9q的基因组扫描一致。基于在我们的研究人群中发现的多个连锁提示区域，很可能不止一个基因影响非裔美国人的结节病易感性。

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.