对409个有精神分裂症的欧洲裔和非裔美国家庭进行全基因组连锁扫描：在合并样本中，8p23.3 - p21.2和11p13.1 - q14.1处存在连锁的提示性证据。
Genomewide linkage scan of 409 European-ancestry and African American families with schizophrenia: suggestive evidence of linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the combined sample.
作者信息
Suarez Brian K, Duan Jubao, Sanders Alan R, Hinrichs Anthony L, Jin Carol H, Hou Cuiping, Buccola Nancy G, Hale Nancy, Weilbaecher Ann N, Nertney Deborah A, Olincy Ann, Green Susan, Schaffer Arthur W, Smith Christopher J, Hannah Dominique E, Rice John P, Cox Nancy J, Martinez Maria, Mowry Bryan J, Amin Farooq, Silverman Jeremy M, Black Donald W, Byerley William F, Crowe Raymond R, Freedman Robert, Cloninger C Robert, Levinson Douglas F, Gejman Pablo V
机构信息
Department of Psychiatry and Genetics, Washington University, St. Louis, MO, USA.
出版信息
Am J Hum Genet. 2006 Feb;78(2):315-33. doi: 10.1086/500272. Epub 2006 Jan 3.
We report the clinical characteristics of a schizophrenia sample of 409 pedigrees--263 of European ancestry (EA) and 146 of African American ancestry (AA)--together with the results of a genome scan (with a simple tandem repeat polymorphism interval of 9 cM) and follow-up fine mapping. A family was required to have a proband with schizophrenia (SZ) and one or more siblings of the proband with SZ or schizoaffective disorder. Linkage analyses included 403 independent full-sibling affected sibling pairs (ASPs) (279 EA and 124 AA) and 100 all-possible half-sibling ASPs (15 EA and 85 AA). Nonparametric multipoint linkage analysis of all families detected two regions with suggestive evidence of linkage at 8p23.3-q12 and 11p11.2-q22.3 (empirical Z likelihood-ratio score [Z(lr)] threshold >/=2.65) and, in exploratory analyses, two other regions at 4p16.1-p15.32 in AA families and at 5p14.3-q11.2 in EA families. The most significant linkage peak was in chromosome 8p; its signal was mainly driven by the EA families. Z(lr) scores >2.0 in 8p were observed from 30.7 cM to 61.7 cM (Center for Inherited Disease Research map locations). The maximum evidence in the full sample was a multipoint Z(lr) of 3.25 (equivalent Kong-Cox LOD of 2.30) near D8S1771 (at 52 cM); there appeared to be two peaks, both telomeric to neuregulin 1 (NRG1). There is a paracentric inversion common in EA individuals within this region, the effect of which on the linkage evidence remains unknown in this and in other previously analyzed samples. Fine mapping of 8p did not significantly alter the significance or length of the peak. We also performed fine mapping of 4p16.3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z(lr) scores was observed for 5p14.1-q12.1, where the maximum Z(lr) increased from 2.77 initially to 3.80 after fine mapping in the EA families.
我们报告了一个包含409个家系的精神分裂症样本的临床特征，其中263个家系为欧洲血统（EA），146个家系为非裔美国人血统（AA），同时还报告了基因组扫描（简单串联重复多态性间隔为9厘摩）及后续精细定位的结果。一个家系需要有一名精神分裂症（SZ）先证者以及该先证者的一名或多名患有SZ或分裂情感性障碍的兄弟姐妹。连锁分析纳入了403对独立的全同胞患病同胞对（ASP）（279对EA和124对AA）以及100对所有可能的半同胞ASP（15对EA和85对AA）。对所有家系进行的非参数多点连锁分析在8p23.3 - q12和11p11.2 - q22.3检测到两个有连锁提示证据的区域（经验性Z对数似然比分数[Z(lr)]阈值≥2.65），在探索性分析中，在AA家系的4p16.1 - p15.32和EA家系的5p14.3 - q11.2检测到另外两个区域。最显著的连锁峰位于8号染色体p区；其信号主要由EA家系驱动。在8p区域，从30.7厘摩至61.7厘摩（遗传疾病研究中心图谱位置）观察到Z(lr)分数>2.0。全样本中的最大证据是在D8S1771（52厘摩处）附近的多点Z(lr)为3.25（相当于Kong - Cox LOD为2.30）；似乎有两个峰，均位于神经调节蛋白1（NRG1）的端粒侧。该区域内的一个臂间倒位在EA个体中很常见，但在本样本及其他先前分析的样本中，其对连锁证据的影响尚不清楚。8p的精细定位并未显著改变峰的显著性或长度。我们还对4p16.3 - p15.2、5p15.2 - q13.3、10p起的精细定位。在5p区域，从最初的2.77增加到精细定位后的3.80。 15.3 - p14、10q25.3 - q26.3和11p13 - q23.3进行了精细定位。在5p14.1 - q12.1观察到Z(lr)分数增加最多，在EA家系中，该区域的最大Z(lr)分数在精细定位后从2.77增加到3.80。
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