Lichtermann D, Hovatta I, Terwilliger J D, Peltonen L, Lönnqvist J
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Am J Psychiatry. 1998 Oct;155(10):1365-75. doi: 10.1176/ajp.155.10.1365.
This study set out to determine, in a homogeneous sample with nationwide coverage in Finland, whether siblings treated for schizophrenia are more often of the same sex than expected by chance, and whether this is especially so when the disorder is transmitted by their fathers.
Finnish social and health insurance files as well as hospital discharge registers were searched for probands with schizophrenia from a birth cohort spanning 30 years. Nuclear families were identified by cross-linkage with the national birth register, and the sex distribution observed in multiply affected sibships was compared with expected distributions by maximum likelihood analysis.
In the subset of multiply affected sibships with one parent who had schizophrenia (84 fathers and 120 mothers), the observed sex distribution did not deviate from the expected pattern. However, a small and marginally significant excess of sex concordance emerged from the total sample of 1,942 sibships in which there were at least two affected members, irrespective of the parents' affection status.
The results indicate that no above-chance sex concordance in sibships multiply affected with paternally transmitted schizophrenia is present in the genetically homogeneous population of Finland. In view of a virtually unbiased and complete ascertainment procedure and sample sizes one to two orders of magnitude larger than those in previous studies, the authors attribute prior findings of such a concordance to sampling artifacts or chance fluctuations and finally conclude that except for regional genetic isolates, there is no epidemiologic evidence that a gene accounting for substantial susceptibility to schizophrenia in a greater proportion of cases resides in the pseudoautosomal region of the sex chromosomes.
本研究旨在确定，在芬兰全国范围内具有同质性的样本中，接受精神分裂症治疗的兄弟姐妹是否比偶然预期的更常为同性，以及当这种疾病由他们的父亲遗传时是否尤其如此。
在跨越30年的出生队列中，从芬兰社会和健康保险档案以及医院出院登记册中搜索精神分裂症先证者。通过与国家出生登记册交叉关联确定核心家庭，并通过最大似然分析将在多个受影响的同胞关系中观察到的性别分布与预期分布进行比较。
在有一位父母患有精神分裂症的多个受影响的同胞关系子集中（84位父亲和120位母亲），观察到的性别分布与预期模式没有偏差。然而，在至少有两名受影响成员的1942个同胞关系的总样本中，出现了少量且略微显著的性别一致性过剩，无论父母的患病状况如何。
结果表明，在芬兰基因同质的人群中，患有由父亲遗传的精神分裂症的多个受影响的同胞关系中，不存在高于偶然概率的性别一致性。鉴于几乎无偏差且完整的确定程序以及样本量比以前的研究大1至2个数量级，作者将先前此类一致性的发现归因于抽样假象或偶然波动，并最终得出结论，除了区域遗传隔离人群外，没有流行病学证据表明在更大比例的病例中，一个导致对精神分裂症有显著易感性的基因位于性染色体的拟常染色体区域。
