Blouin J L, Dombroski B A, Nath S K, Lasseter V K, Wolyniec P S, Nestadt G, Thornquist M, Ullrich G, McGrath J, Kasch L, Lamacz M, Thomas M G, Gehrig C, Radhakrishna U, Snyder S E, Balk K G, Neufeld K, Swartz K L, DeMarchi N, Papadimitriou G N, Dikeos D G, Stefanis C N, Chakravarti A, Childs B, Housman D E, Kazazian H H, Antonarakis S, Pulver A E
Division of Medical Genetics, University of Geneva Medical School and Cantonal Hospital, Switzerland.
Nat Genet. 1998 Sep;20(1):70-3. doi: 10.1038/1734.
Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).
精神分裂症是一种以精神病性症状为特征的常见疾病；诊断标准已经确立。家族、双生子和收养研究表明，遗传因素和环境因素均影响易感性（遗传度约为71%；参考文献2），然而，对于精神分裂症的病因知之甚少。临床和家族研究提示病因的异质性。此前，我们报道22号、3号和8号染色体上的区域可能与精神分裂症易感性相关，并且合作研究为8号和22号染色体上的区域提供了一些支持（参考文献9 - 13）。我们在此展示一项针对精神分裂症易感基因座（SSL）的全基因组扫描，使用了54个多重家系中的452个微卫星标记。非参数连锁（NPL）分析为13q32染色体上的一个SSL提供了显著证据（NPL评分 = 4.18；P = 0.00002），并为8p21 - 22染色体上的另一个SSL提供了提示性证据（NPL = 3.64；P = 0.0001）。参数连锁分析为这些SSL提供了额外支持。8号染色体上的连锁证据比13号染色体上的弱，因此8号染色体更有可能是假阳性连锁。在14q13（NPL = 2.57；P = 0.005）、7q11（NPL = 2.50，P = 0.007）和22q11（NPL = 2.42，P = 0.009）染色体上发现了其他假定的SSL。在51个多重家系的后续样本中尝试验证13q和8p染色体上提示性的SSL。该分析证实了13q14 - q33中的SSL（NPL = 2.36，P = 0.007），并支持了8p22 - p21中的SSL（NPL = 1.95，P = 0.023）。
