From the Department of Psychiatry and the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond; the Center for Primary Health Care Research, Lund University, Malmö, Sweden; and the Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Am J Psychiatry. 2018 Nov 1;175(11):1137-1144. doi: 10.1176/appi.ajp.2018.17111251. Epub 2018 Jul 19.
The authors examined the heritability of treated major depression in a twin and full/half-sibling design, to describe key genetic epidemiological features of major depression and to determine which clinical indices of genetic liability optimally predict risk of depression in relatives.
The authors examined all treated cases of major depression in Sweden recorded in inpatient, specialist, and primary care registries and, using OpenMx, estimated the etiologic role of genetic and environmental factors from monozygotic and dizygotic twin pairs and full and half siblings reared together and apart (total N=1,718,863 pairs). Eight indices of genetic risk were examined in 875,010 proband-relative pairs.
The heritability of major depression in men and women was estimated at 0.41 (95% CI=0.21, 0.49) and 0.49 (95% CI=0.31, 0.56), respectively, in the twin design and 0.36 (95% CI=0.31, 0.38) and 0.51 (95% CI=0.51, 0.53), respectively, in the independent full/half-sibling design. The best estimate of the correlation in genetic effects across sexes was 0.89 (95% CI=0.87, 0.91). The results also showed evidence of modest shared environmental effects (0.02-0.05). Seven of the eight indices predicted risk for major depression in relatives, with stronger effects in those more closely related. The strongest indices were early age at onset, recurrence, comorbid anxiety disorder, and measures of clinical severity.
In a large national sample, the heritability of major depression was similar when estimated from twin and full/half-sibling designs. The heritability of major depression was greater in women than in men, with the two sexes sharing most but not all genetic risk factors. In affected individuals, genetic risk for major depression could be meaningfully assessed from commonly available clinical indices.
作者通过双胞胎和全/半同胞设计，研究了经治疗的重度抑郁症的遗传性，以描述重度抑郁症的关键遗传流行病学特征，并确定哪些遗传易感性的临床指标能最佳预测亲属患抑郁症的风险。
作者检查了瑞典所有在住院、专科和初级保健登记册中记录的经治疗的重度抑郁症病例，并使用 OpenMx 从同卵双胞胎和异卵双胞胎以及一起和分开抚养的全同胞和半同胞对中估计遗传和环境因素的病因作用（总共 N=1,718,863 对）。在 875,010 个先证者-亲属对中检查了 8 个遗传风险指标。
在双胞胎设计中，男性和女性重度抑郁症的遗传性估计值分别为 0.41（95% CI=0.21, 0.49）和 0.49（95% CI=0.31, 0.56），在独立的全/半同胞设计中分别为 0.36（95% CI=0.31, 0.38）和 0.51（95% CI=0.51, 0.53）。性别间遗传效应相关性的最佳估计值为 0.89（95% CI=0.87, 0.91）。结果还表明存在适度的共享环境效应（0.02-0.05）。八个指标中的七个预测了亲属患重度抑郁症的风险，与亲属关系越近，预测效果越强。最强的指标是发病年龄较早、复发、伴发焦虑障碍和临床严重程度的测量。
在一个大型的全国性样本中，从双胞胎和全/半同胞设计中估计的重度抑郁症遗传性相似。女性的重度抑郁症遗传性高于男性，两性共享大部分但不是所有的遗传风险因素。在受影响的个体中，可从常用的临床指标中对重度抑郁症的遗传风险进行有意义的评估。
