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瑞典双胞胎中无帕金森病遗传证据。

No evidence for heritability of Parkinson disease in Swedish twins.

作者信息

Wirdefeldt Karin, Gatz Margaret, Schalling Martin, Pedersen Nancy L

机构信息

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

出版信息

Neurology. 2004 Jul 27;63(2):305-11. doi: 10.1212/01.wnl.0000129841.30587.9d.

Abstract

BACKGROUND

Although several genes are implicated in Parkinson disease (PD), they explain only a small fraction of cases. The etiology of most cases is yet unknown.

OBJECTIVE

To evaluate heritability of PD in same-sexed and opposite-sexed twin pairs in the Swedish Twin Registry (STR).

METHODS

All twins in the STR born in 1950 or earlier and alive in 1998 (n = 50,150) were included. The authors screened 33,780 twins in 14,082 pairs for PD by telephone interviews and linked the STR to the Swedish Inpatient Discharge Register. Two hundred forty-seven twins with self-reported PD or a PD diagnosis in the Inpatient Discharge Register (called "possible PD") and 517 twins who reported parkinsonian symptoms or use of antiparkinsonian medication ("suspected parkinsonism or movement disorder") were identified.

RESULTS

For possible PD, there were only two concordant pairs, both female dizygotic. Similarly, concordances were low in all zygosity groups when the definition of affected was expanded to include twins with suspected parkinsonism or movement disorder in addition to possible PD. Sex differences in the relative importance of genetic and environmental effects were indicated with a marginally larger familial component in women. The best-fitting structural equation model included only environmental components of variance.

CONCLUSIONS

These results suggest that environmental factors are most important in the etiology of PD. Compared with other complex diseases, the importance of genetic effects in PD is notably low. The preponderance of discordant twin pairs provides an ideal material for studying environmental risk factors and potential genotype-by-environment interaction.

摘要

背景

尽管有多个基因与帕金森病(PD)相关,但它们仅能解释一小部分病例。大多数病例的病因尚不清楚。

目的

评估瑞典双胞胎登记处(STR)中同性和异性双胞胎对PD的遗传度。

方法

纳入STR中1950年或更早出生且1998年仍在世的所有双胞胎(n = 50,150)。作者通过电话访谈对14,082对双胞胎中的33,780名进行了PD筛查,并将STR与瑞典住院患者出院登记处相链接。识别出247名自我报告患有PD或在住院患者出院登记处有PD诊断(称为“可能的PD”)的双胞胎,以及517名报告有帕金森症状或使用抗帕金森药物(“疑似帕金森症或运动障碍”)的双胞胎。

结果

对于可能的PD,仅有两对一致的双胞胎,均为女性异卵双胞胎。同样,当将受影响的定义扩大到除可能的PD外还包括疑似帕金森症或运动障碍的双胞胎时,所有合子类型组的一致性都很低。遗传和环境效应相对重要性的性别差异表明,女性的家族成分略大。最佳拟合结构方程模型仅包括方差的环境成分。

结论

这些结果表明环境因素在PD的病因中最为重要。与其他复杂疾病相比,遗传效应在PD中的重要性明显较低。不一致的双胞胎对占优势为研究环境风险因素和潜在的基因-环境相互作用提供了理想材料。

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