The heritability of bipolar affective disorder and the genetic relationship to unipolar depression
The heritability of bipolar affective disorder and the genetic relationship to unipolar depression
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DOI：
10.1001/archpsyc.60.5.497
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发表时间：
2003-05-01
影响因子：
--
通讯作者：
Cardno, A
中科院分区：
文献类型：
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作者：
McGuffin, P;Rijsdijk, F;Cardno, A
背景：双相情感障碍(BPD)的双胞胎研究要么规模较小，要么没有明确的诊断标准。关于单相抑郁(UPD)的病因重叠，很少有遗传模型拟合和分析。方法：67对双胞胎，30对同卵和37对双生子，先证者有BPD，并根据DSM-IV标准进行终生诊断。应用单变量模型估计加性遗传效应和环境效应的贡献。然后将双相数据与68对单合子和109对双合子的数据结合起来，其中先证者有UPD。结果：BPD的遗传度估计为85%(95%可信区间[CI]，0.73~0.93)，广义一致性估计为89%(95%CI，0.61~1.0)，未发现共同的环境效应。双阈值模型不能令人满意。相关风险模型拟合结果显示，躁狂与抑郁的遗传相关系数为0.65(95%CI，0.58~0.75)，非家庭环境相关系数为0.59(95%CI，0.15~0.84)。结论：根据DSM-IV的定义，BPD具有高度的遗传性。躁狂症和抑郁症之间有实质性的遗传和非共有的环境相关性，但躁狂症易感性的大部分遗传差异是与躁狂综合征有关的。
Background: Twin studies of bipolar affective disorder (BPD) have either been small or have not used explicit diagnostic criteria. There has been little use of genetic model fitting and no analyses to explore the etiological overlap with unipolar depression (UPD).Methods: Sixty-seven twin pairs, 30 monozygotic and 37 dizygotic, in which the proband had BPD were ascertained, and lifetime diagnoses were made using DSM-IV criteria. Univariate models were applied to estimate the contribution of additive genetic and environmental effects. Bipolar data were then combined with those from 68 monozygotic and 109 dizygotic pairs in which the proband had UPD. Two models were explored: a classic 2-threshold approach, in which BPD and UPD occupy the same continuum of liability but differ in severity, and a correlated liability model of mania and depression.Results: Heritability of BPD was estimated at 85% (95% confidence interval [CI], 0.73-0.93) using narrow concordance and 89% (95% CI, 0.61-1.0) using broad concordance, with no shared environmental effects detected. A 2-threshold model was an unsatisfactory fit. Fitting a correlated liability model revealed a genetic correlation of 0.65 (95% CI, 0.58-0.75) between mania and depression and a correlation of 0.59 (95% CI, 0.15-0.84) for nonfamilial environment. Approximately 71% of the genetic variance for mania was not shared with depression.Conclusions: As defined by the DSM-IV, BPD is highly heritable. There are substantial genetic and nonshared environmental correlations between mania and depression, but most of the genetic variance in liability to mania is specific to the manic syndrome.