Sallis Hannah, Evans Jonathan, Wootton Robyn, Krapohl Eva, Oldehinkel Albertine J, Davey Smith George, Paternoster Lavinia
MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 2BN, UK.
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
BMC Psychiatry. 2017 Aug 31;17(1):321. doi: 10.1186/s12888-017-1484-y.
Despite many attempts to understand the genetic architecture of depression, little progress has been made. The majority of these studies, however, have been carried out in adults and do not account for the potential influence of development.
The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal pregnancy cohort which recruited participants between April 1991 and December 1992. Analyses were replicated in two independent European cohorts. Genome-wide complex trait analysis (GCTA) software was used to investigate SNP-heritability (h) of depression across adolescence, the role of puberty was investigated by stratifying these estimates according to pubertal onset. Genome-wide association studies were performed to identify genetic variants associated with depression at different stages of development.
Heritability was estimated between the ages of 11 and 18 with sample sizes ranging from 3289 to 5480. Heritability was low with an apparent peak was found at age 13 (h = 0.17, p = 0.006). Confidence intervals around these estimates suggest an upper-bound to h of around 30%. A variant located on chromosome 7 was found to be associated with depressive symptoms at age 13 in ALSPAC (rs138191010: β = 0.142, p = 2.51 × 10), although this was not replicated.
Although power is a potential limitation, the observed patterns provide interesting hypotheses surrounding the heritability of depression at different developmental stages. We found substantially lower estimates for depressive symptoms at age 11 (0.07) compared to those previously estimated in adults (0.21). We also found a peak in heritability at age 13. These findings suggest environmental factors are likely to be more important in the aetiology of depressive symptoms in early adolescence than in adulthood.
尽管人们多次尝试了解抑郁症的遗传结构，但进展甚微。然而，这些研究大多是在成年人中进行的，并未考虑发育的潜在影响。
雅芳亲子纵向研究（ALSPAC）是一个纵向妊娠队列研究，于1991年4月至1992年12月招募参与者。分析在两个独立的欧洲队列中重复进行。使用全基因组复杂性状分析（GCTA）软件研究整个青春期抑郁症的单核苷酸多态性遗传力（h），通过根据青春期开始情况对这些估计值进行分层来研究青春期的作用。进行全基因组关联研究以确定在发育不同阶段与抑郁症相关的基因变异。
在11至18岁之间估计遗传力，样本量从3289至5480不等。遗传力较低，在13岁时出现明显峰值（h = 0.17，p = 0.006）。这些估计值的置信区间表明h的上限约为30%。在ALSPAC研究中，发现位于7号染色体上的一个变异与13岁时的抑郁症状相关（rs138191010：β = 0.142，p = 2.51×10），尽管未得到重复验证。
尽管样本量可能是一个潜在限制，但观察到的模式为不同发育阶段抑郁症的遗传力提供了有趣的假设。我们发现11岁时抑郁症状的估计值（0.07）远低于先前在成年人中估计的值（0.21）。我们还发现遗传力在13岁时达到峰值。这些发现表明，在青春期早期，环境因素在抑郁症状的病因学中可能比在成年期更重要。
