Kendler Kenneth S, Ohlsson Henrik, Sundquist Jan, Sundquist Kristina
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Mol Psychiatry. 2025 Apr 17. doi: 10.1038/s41380-025-03022-z.
We seek to clarify the impact of the Genetic Aptitude for Educational Attainment (GAEA) on risk for 10 psychiatric disorders divided into 4 groups: Internalizing, Externalizing, Eating/Compulsive and Psychotic. Educational attainment and psychiatric and substance use disorder information were obtained from national Swedish registries. GAEA and disorder-specific family genetic risk score (FGRS) were calculated from extended pedigrees. In males, information on IQ and resilience was obtained from the Swedish conscript registry. Affected individuals were born in Sweden from 1973-1995 to Swedish born parents. Controlling for disorder specific FGRS, GAEA were negatively and substantially associated with risk for externalizing and internalizing disorders, minimally associated with psychotic disorder risk and positively and modestly associated with risk for eating/compulsive disorders. While the majority of GAEA effect on risk for externalizing disorders was mediated through impact on IQ, for internalizing disorders, mediation was largely through resilience. For externalizing and internalizing disorders, interactions between GAEA and disorder specific FGRS were robust and negative - the slope of disorder risk with increasing genetic liability was steepest in those with low GAEA. For eating disorders, interactions were modest and positive -the slope of risk with increasing genetic liability being steepest in individuals with high GAEA. We found that the impact of GAEA on risk for psychiatric and substance can be substantial and varies widely across disorders in magnitude, direction, and mediation. GAEA also often interacts, sometimes robustly, with disorder specific genetic risk factors. Comprehensive risk models for psychiatric disorders should consider the inclusion of GAEA.
我们试图阐明教育成就遗传能力（GAEA）对10种精神疾病风险的影响，这些疾病分为4组：内化性、外化性、饮食/强迫性和精神病性。教育成就以及精神疾病和物质使用障碍信息来自瑞典国家登记处。GAEA和特定疾病的家族遗传风险评分（FGRS）是根据扩展谱系计算得出的。在男性中，智商和复原力信息来自瑞典征兵登记处。受影响个体于1973年至1995年在瑞典出生，其父母也出生在瑞典。在控制特定疾病的FGRS后，GAEA与外化性和内化性疾病风险呈负相关且相关性显著，与精神病性障碍风险相关性最小，与饮食/强迫性疾病风险呈正相关且相关性适中。虽然GAEA对外化性疾病风险的大部分影响是通过对智商的影响介导的，但对于内化性疾病，介导作用主要是通过复原力。对于外化性和内化性疾病，GAEA与特定疾病的FGRS之间的相互作用很强且为负——在GAEA低的人群中，随着遗传易感性增加，疾病风险的斜率最陡。对于饮食失调，相互作用适中且为正——在GAEA高的个体中，随着遗传易感性增加，风险斜率最陡。我们发现，GAEA对精神疾病和物质使用风险的影响可能很大，并且在不同疾病之间，其在大小、方向和介导作用方面差异很大。GAEA还经常与特定疾病的遗传风险因素相互作用，有时相互作用很强。精神疾病的综合风险模型应考虑纳入GAEA。
