Familial transmission of schizophrenia in Palau: A 20-year genetic epidemiological study in three generations.
Familial transmission of schizophrenia in Palau: A 20-year genetic epidemiological study in three generations.
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帕劳精神分裂症的家族传播：一项为期 20 年的三代遗传流行病学研究。
DOI：
10.1002/ajmg.b.31171
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Faraone,StephenV
中科院分区：
文献类型：
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作者：
Myles-Worsley,Marina;Tiobech,Josepha;Blailes,Francisca;Middleton,FrankA;Vinogradov,Sophia;Byerley,William;Faraone,StephenV
我们对帕劳孤立人群中的精神分裂症和其他精神病 (SCZ) 的遗传流行病学研究已经持续了 20 年。第一个十年的结果表明，帕劳的 SCZ 患病率较高，并且病例聚集在经过几个世纪的同族通婚而非近亲婚姻后，通过复杂的遗传关系相互关联的扩展的多代谱系。我们第二个十年的研究将数据收集范围扩大到了第三代年轻高危 (HR) 帕劳人，其目的是确定疾病代际传播的重要预测因素。我们的研究结果表明，家庭负担程度和性别对生殖健康的影响是 SCZ 传播风险的重要调节因素。在 45 个不同的多重家庭中，我们确定了 10 个高密度 (HD) 帕劳家庭，每个家庭有 7-29 个 SCZ 病例，其中包含帕劳 260 个 SCZ 病例的一半和 113 个 SCZ 病例的 80%，有一个或多个受影响的一级亲属，表明家族负荷是帕劳 SCZ 的主要危险因素。属于多重受影响同胞的病例比具有受影响父母的病例更常见。此外，只有 6/38 的多重受影响同胞有受影响的父母，有力的证据表明许多未受影响的父母是易感基因的必然携带者。尽管受影响的男性的生殖健康状况显着下降，但 30% 的少数成为父亲的人将 SCZ 传染给后代的可能性是受影响的母亲的两倍。随着它们的进化，这些 HD 家族可以帮助阐明预测 SCZ 代际传播的遗传机制。 © 2011 Wiley-Liss, Inc.
Our genetic epidemiological studies of schizophrenia and other psychotic disorders (SCZ) in the isolated population of Palau have been ongoing for 20 years. Results from the first decade showed that Palau has an elevated prevalence of SCZ and that cases cluster in extended multigenerational pedigrees interconnected via complex genetic relationships after centuries of endogamous, but not consanguineous, marriages. The aim of our second decade of research, which extended data collection into a third generation of young, high‐risk (HR) Palauans, was to identify significant predictors of intergenerational transmission of illness. Our findings revealed that degree of familial loading and gender effects on reproductive fitness are important modifiers of risk for transmission of SCZ. Among 45 distinct multiplex families, we identified 10 high‐density (HD) Palauan families, each with 7–29 SCZ cases, which contain half of Palau's 260 SCZ cases and 80% of the 113 SCZ cases with one or more affected first‐degree relatives, indicating that familial loading is a major risk factor for SCZ in Palau. Cases that belong to multiply affected sibships are more common than cases with an affected parent. Furthermore, only 6/38 multiply affected sibships have an affected parent, strong evidence that many unaffected parents are obligate carriers of susceptibility genes. Although reproductive fitness is dramatically reduced in affected males, the 30% minority who do become fathers are twice as likely as affected mothers to transmit SCZ to an offspring. As they evolve, these HD families can help to elucidate the genetic mechanisms that predict intergenerational transmission of SCZ. © 2011 Wiley‐Liss, Inc.