A continuum of genetic liability for minor and major depression.
A continuum of genetic liability for minor and major depression.
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DOI：
10.1038/tp.2017.99
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发表时间：
2017-05-16
影响因子：
6.8
通讯作者：
Nyholt DR
中科院分区：
文献类型：
--
作者：
Corfield EC;Yang Y;Martin NG;Nyholt DR
最近一项大型全基因组关联 (GWA) 研究（分析了 130 620 例重度抑郁症病例和 347 620 例对照）成功确定了第一个与欧洲人重度抑郁症密切相关的单核苷酸多态性 (SNP) 位点，这证实需要大量样本来确定抑郁症的风险位点。鉴于重度抑郁症 (MDD) 和不太严重的轻度抑郁症 (MiDD) 之间的表型相似性，我们假设扩大病例定义以包括 MiDD 可能是增加抑郁症 GWA 研究样本量的有效方法。通过分析两个大型双胞胎队列，我们发现轻度抑郁症和重度抑郁症处于同一遗传连续体上，重度抑郁症更严重，但在病因学上与轻度抑郁症没有区别。此外，我们估计在一组老年人（50-92 岁）中，轻度抑郁症的遗传率为 37%，重度抑郁症的遗传率为 46%，轻度或重度抑郁症的遗传率为 48%。然而，在年轻人（23-38 岁）队列中，轻度或重度抑郁症的遗传率估计为 40%。此外，在我们的澳大利亚 GWA 数据集中，两个名义上与重度抑郁症相关的稳健的重度抑郁症风险 SNP 提供了与轻度或重度抑郁症相关的更重要的证据。因此，扩大 GWA 研究中的病例表型以包括阈下定义，例如 MiDD，应该有助于识别抑郁症的其他遗传风险位点。
The recent success of a large genome-wide association (GWA) study—analysing 130 620 major depression cases and 347 620 controls—in identifying the first single-nucleotide polymorphism (SNP) loci robustly associated with major depression in Europeans confirms that immense sample sizes are required to identify risk loci for depression. Given the phenotypic similarity between major depressive disorder (MDD) and the less severe minor depressive disorder (MiDD), we hypothesised that broadening the case definition to include MiDD may be an efficient approach to increase sample sizes in GWA studies of depression. By analysing two large twin pair cohorts, we show that minor depression and major depression lie on a single genetic continuum, with major depression being more severe but not aetiologically distinct from minor depression. Furthermore, we estimate heritabilities of 37% for minor depression, 46% for major depression and 48% for minor or major depression in a cohort of older adults (aged 50–92). However, the heritability of minor or major depression was estimated at 40% in a cohort of younger adults (aged 23–38). Moreover, two robust major depression-risk SNPs nominally associated with major depression in our Australian GWA data set produced more significant evidence for association with minor or major depression. Hence, broadening the case phenotype in GWA studies to include subthreshold definitions, such as MiDD, should facilitate the identification of additional genetic risk loci for depression.
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影响因子：
3
作者：
Boker S;Neale M;Maes H;Wilde M;Spiegel M;Brick T;Spies J;Estabrook R;Kenny S;Bates T;Mehta P;Fox J
通讯作者：
Fox J
影响因子：
11
作者：
Bosker, F. J.;Hartman, C. A.;Nolen, W. A.
通讯作者：
Nolen, W. A.
影响因子：
6.8
作者：
AKAIKE, H
通讯作者：
AKAIKE, H
影响因子：
6.6
作者：
Lewinsohn, PM;Klein, DN;Rohde, P
通讯作者：
Rohde, P
DOI：
10.1375/twin.4.2.73
发表时间：
2001-04-01
期刊：
Twin research : the official journal of the International Society for Twin Studies
影响因子：
--
作者：
Heath, A C;Howells, W;Martin, N G
通讯作者：
Martin, N G