Wiener H W, Klei L, Irvin M D, Perry R T, Aliyu M H, Allen T B, Bradford L D, Calkins M E, Devlin B, Edwards N, Gur R E, Gur R C, Kwentus J, Lyons P D, McEvoy J P, Nasrallah H A, Nimgaonkar V L, O'Jile J, Santos A B, Savage R M, Go R C P
University of Alabama at Birmingham, School of Public Health, Dept. of Epidemiology, 1665 University Blvd., RPHB, Birmingham, AL 35294-0022, USA.
Schizophr Res. 2009 Apr;109(1-3):70-9. doi: 10.1016/j.schres.2009.02.007. Epub 2009 Mar 5.
While many studies have sought a window into the genetics of schizophrenia, few have focused on African-American families. An exception is the Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS), which seeks to identify novel and known risk variation for schizophrenia by genetic analyses of African-American families. We report a linkage study of diagnostic status in 217 African-American families using the Illumina Linkage Panel. Due to assumed incomplete and time-dependent penetrance, we performed linkage analysis using two different treatments of diagnosis: (1) treating both affected and unaffected individuals as informative for linkage (using the program SIBPAL) and (2) treating only affected individuals as informative (using the program MERLIN). We also explore three definitions of affected status: narrowly defined schizophrenia; one broadened to include schizoaffective disorder; and another including all diagnoses indicating psychosis. Several regions show a decrease in the evidence for linkage as the definition broadens 8q22.1 (rs911, 99.26 cM; SIBPAL p-value [p] goes from 0.006 to 0.02), 16q24.3 (rs1006547, 130.48 cM; p from 0.00095 to 0.0085), and 20q13.2 (rs1022689, 81.73 cM; p from 0.00015 to 0.032). One region shows a substantial increase in evidence for linkage, 11p15.2 (rs722317, 24.27 cM; p from 0.0022 to 0.0000003); MERLIN results support the significance of the SIBPAL results (p=0.00001). Our linkage results overlap two broad, previously-reported linkage regions: 8p23.3-p12 found in studies sampling largely families of European ancestry; and 11p11.2-q22.3 reported by a study of African-American families. These results should prove quite useful for uncovering loci affecting risk for schizophrenia.
虽然许多研究都在探寻了解精神分裂症遗传学特征的途径，但很少有研究聚焦于非裔美国家庭。“非裔美国人精神分裂症风险探索项目”（PAARTNERS）是个例外，该项目旨在通过对非裔美国家庭进行基因分析，来识别精神分裂症新的和已知的风险变异。我们报告了一项使用Illumina连锁分析面板对217个非裔美国家庭的诊断状况进行的连锁研究。由于假定存在不完全和时间依赖性的外显率，我们使用两种不同的诊断处理方法进行连锁分析：（1）将患病个体和未患病个体均视为对连锁分析有信息价值（使用SIBPAL程序）；（2）仅将患病个体视为有信息价值（使用MERLIN程序）。我们还探讨了三种患病状态的定义：狭义的精神分裂症；一种拓宽至包括分裂情感性障碍；另一种包括所有表明精神病的诊断。随着定义的拓宽，几个区域的连锁证据减少，如8q22.1（rs911，99.26厘摩；SIBPAL p值从0.006变为0.02）、16q24.3（rs1006547，130.48厘摩；p值从0.00095变为0.0085）以及20q13.2（rs1022689，81.73厘摩；p值从0.00015变为0.032）。有一个区域的连锁证据大幅增加，即11p15.2（rs722317，24.27厘摩；p值从0.0022变为0.0000003）；MERLIN的结果支持了SIBPAL结果的显著性（p = 0.00001）。我们的连锁结果与之前报告的两个广泛的连锁区域重叠：在主要对欧洲血统家庭进行抽样的研究中发现的8p23.3 - p12；以及一项针对非裔美国家庭的研究报告的11p11.2 - q22.3。这些结果对于揭示影响精神分裂症风险的基因座应该非常有用。
