Freedman R, Leonard S, Olincy A, Kaufmann C A, Malaspina D, Cloninger C R, Svrakic D, Faraone S V, Tsuang M T
Department of Psychiatry, Denver VA Medical Center and University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Am J Med Genet. 2001 Dec 8;105(8):794-800. doi: 10.1002/ajmg.10100.
Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the alpha 7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci.
由于精神分裂症的高患病率和散发性家族传递，人们认为它具有复杂的遗传方式。不同研究中在不同染色体上发现的连锁现象证实了这一假设。目前尚不清楚这些发现代表的是异质性遗传（即不同种族群体通过不同的主要基因效应遗传疾病）还是多基因遗传（即受影响个体继承了几种常见的遗传异常）。因此，本研究在一个全国性收集的欧美裔和非裔美国人样本中，检查了精神分裂症在不同基因位点的遗传情况。77个家庭先前已针对美国国立精神卫生研究所精神分裂症遗传学计划的458个标记进行了基因分型。初始遗传分析测试了一个显性模型，将精神分裂症和抑郁型分裂情感障碍作为受影响的表型。这些家庭在15号染色体q14区域显示出一个全基因组显著连锁（Z = 3.97），该区域位于先前与α7 - 烟碱受体基因连锁区域的1厘摩范围内。10号染色体p13区域显示出提示性连锁（Z = 2.40）。另外六个区域（6号染色体q21、9号染色体q32、13号染色体q32、15号染色体q24、17号染色体p12、20号染色体q13）呈阳性，两个种族群体之间差异不大。每个家庭通过两个基因传递精神分裂症的概率大于每个基因独立分离组合所预期的概率。双性状位点连锁分析支持这样一种模型，即与精神分裂症相关的遗传等位基因在一般人群中相对常见，受影响个体通过至少两个不同位点继承患病风险。
