Kendler Kenneth S, Abrahamsson Linda, Ohlsson Henrik, Sundquist Jan, Sundquist Kristina
Virginia Institute for Psychiatric and Behavioral Genetics and Department of Psychiatry, Virginia Commonwealth University, Richmond, (Kendler); Center for Primary Health Care Research, Lund University, Malmö, Sweden (Abrahamsson, Ohlsson, J. Sundquist, K. Sundquist); Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York (J. Sundquist, K. Sundquist).
Am J Psychiatry. 2022 Sep;179(9):640-649. doi: 10.1176/appi.ajp.21111110.
To clarify, using an extended adoption design, the sources of parent-offspring transmission for anxiety disorder (AD) and its major subforms and their familial cross-generational relationship with major depression (MD).
Offspring (born 1960-1992) and their parents, from six family types (intact, not-lived-with biological father or mother, lived-with step-father or step-mother, and adoptive), were ascertained from Swedish national samples. Diagnoses were obtained from national medical registers. We assessed three sources of parent-child resemblance: genes plus rearing, genes only, and rearing only. To test comorbidity effects, single diagnoses were assigned in comorbid cases based on frequency and recency.
For AD to AD parent-child transmission, best-estimate tetrachoric correlations for the three types of parent-offspring relationships genes plus rearing, genes only, and rearing only-equaled +0.16 (95% CI=0.16, 0.16), +0.12 (95% CI=0.10, 0.13), and +0.06 (95% CI=0.04, 0.07), respectively, with broadly similar results for MD to MD transmission. Cross-disorder cross-generation correlations were modestly lower, with genetic and rearing correlations for AD and MD estimated at +0.83 (95% CI=0.76, 0.90) and +0.83 (95% CI=0.69, 0.96), respectively. Analyses for panic disorder and generalized anxiety disorder (GAD) produced comparable findings, with the genetic correlation with MD modestly higher for generalized anxiety disorder than panic disorder. Applying a diagnostic hierarchy to comorbid cases resulted in a decline in cross-disorder cross-generation transmission with the estimated genetic correlation equaling +0.46 (95% CI=0.30, 0.62).
For AD and its major subforms, cross-generational transmission includes both genetic and rearing effects. In traditional analyses, AD and MD demonstrate highly correlated genetic and rearing effects. The genetic correlation weakened when applying a diagnostic hierarchy.
采用扩展收养设计,阐明焦虑症(AD)及其主要亚型的亲子传递来源,以及它们与重度抑郁症(MD)的家族跨代关系。
从瑞典全国样本中确定了六种家庭类型(完整家庭、未与亲生父亲或母亲同住、与继父或继母同住以及收养家庭)的后代(出生于1960年至1992年)及其父母。诊断信息来自国家医疗登记处。我们评估了亲子相似性的三个来源:基因加养育、仅基因和仅养育。为了测试共病效应,在共病病例中根据频率和近期性分配单一诊断。
对于AD到AD的亲子传递,三种亲子关系类型(基因加养育、仅基因和仅养育)的最佳估计四分相关系数分别为+0.16(95%CI = 0.16, 0.16)、+0.12(95%CI = 0.10, 0.13)和+0.06(95%CI = 0.04, 0.07),MD到MD传递的结果大致相似。跨障碍跨代相关系数略低,AD和MD的遗传和养育相关系数估计分别为+0.83(95%CI = 0.76, 0.90)和+0.83(95%CI = 0.69, 0.96)。惊恐障碍和广泛性焦虑症(GAD)的分析产生了类似的结果,广泛性焦虑症与MD的遗传相关性略高于惊恐障碍。对共病病例应用诊断层次结构导致跨障碍跨代传递下降,估计遗传相关系数为+0.46(95%CI = 0.30, 0.62)。
对于AD及其主要亚型,跨代传递包括遗传和养育效应。在传统分析中,AD和MD表现出高度相关的遗传和养育效应。应用诊断层次结构时,遗传相关性减弱。