Epidemiology and Heritability of Major Depressive Disorder, Stratified by Age of Onset, Sex, and Illness Course in Generation Scotland: Scottish Family Health Study (GS: SFHS)
Epidemiology and Heritability of Major Depressive Disorder, Stratified by Age of Onset, Sex, and Illness Course in Generation Scotland: Scottish Family Health Study (GS: SFHS)
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DOI：
10.1371/journal.pone.0142197
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发表时间：
2015-11-16
期刊：
影响因子：
3.7
通讯作者：
McIntosh, Andrew M.
中科院分区：
文献类型：
--
作者：
Fernandez-Pujals, Ana Maria;Adams, Mark James;McIntosh, Andrew M.
重度抑郁症 (MDD) 的遗传率估计为 37%，主要基于依赖有争议假设的双胞胎研究。最近，MDD 的遗传力在来自瑞典、芬兰和中国等登记的大量人群中进行了估计。基于家族的设计利用了许多不同的关系，并提供了估计遗传力的替代方法。苏格兰一代：苏格兰家庭健康研究 (GS:SFHS) 是一项大型 (n = 20,198)、以家庭为基础的人口研究，旨在确定常见疾病（包括重度抑郁症）的遗传决定因素。 2706 人被 SCID 诊断为 MDD，占队列的 13.5%，从中我们推断出人群患病率为 12.2%（95% 可信区间：11.4% 至 13.1%）。 MDD 风险增加与女性、因残疾而失业、目前吸烟、以前饮酒以及生活在社会贫困程度较高的地区有关。根据谱系模型估计，GS:SFHS 中 MDD 的遗传力在 28% 至 44% 之间。对MDD在性别、发病年龄和病程之间的遗传相关性进行了检查，结果显示出很强的遗传相关性。男性和女性MDD的遗传相关性为0.75（0.43至0.99）；早期（40 岁）发病之间的比率为 0.85（0.66 至 0.98）；单发性和复发性发作性疾病病程之间的比率为 0.87（0.72 至 0.98）。我们发现，复发性MDD病程的遗传力显着大于单一MDD病程的遗传力。该研究证实，遗传对抑郁症有中等程度的影响，共同家庭环境的影响很小（方差比例 = 0.07，CI：0.01 至 0.15），并支持 MDD 与先前确定的危险因素之间的关系。这项研究没有发现对性别、发病年龄或病程造成的 MDD 遗传差异的有力支持。然而，我们发现复发性 MDD 病程和单一 MDD 病程之间的遗传力存在有趣的差异。这些发现使 GS:SFHS 成为 MDD 基因研究的一个有价值的队列。
The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier ( age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.