State Key Laboratory of Microbial metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Transl Psychiatry. 2022 Aug 26;12(1):347. doi: 10.1038/s41398-022-02041-6.
Although there are pronounced sex differences for psychiatric disorders, relatively little has been published on the heterogeneity of sex-specific genetic effects for these traits until very recently for adults. Much less is known about children because most psychiatric disorders will not manifest until later in life and existing studies for children on psychiatric traits such as cognitive functions are underpowered. We used results from publicly available genome-wide association studies for six psychiatric disorders and individual-level data from the Adolescent Brain Cognitive Development (ABCD) study and the UK Biobank (UKB) study to evaluate the associations between the predicted polygenic risk scores (PRS) of these six disorders and observed cognitive functions, behavioral and brain imaging traits. We further investigated the mediation effects of the brain structure and function, which showed heterogeneity between males and females on the correlation between genetic risk of schizophrenia and fluid intelligence. There was significant heterogeneity in genetic associations between the cognitive traits and psychiatric disorders between sexes. Specifically, the PRSs of schizophrenia of boys showed stronger correlation with eight of the ten cognitive functions in the ABCD data set; whereas the PRSs of autism of females showed a stronger correlation with fluid intelligence in the UKB data set. Besides cognitive traits, we also found significant sexual heterogeneity in genetic associations between psychiatric disorders and behavior and brain imaging. These results demonstrate the underlying early etiology of psychiatric disease and reveal a shared and unique genetic basis between the disorders and cognition traits involved in brain functions between the sexes.
尽管精神障碍存在明显的性别差异，但直到最近，针对这些特征的特定性别遗传效应的异质性才在成人中得到了相对较少的研究。对于儿童，人们了解得更少，因为大多数精神障碍要到生命后期才会显现，而针对儿童精神障碍特征（如认知功能）的现有研究则没有足够的效力。我们使用了六项精神障碍的公开全基因组关联研究结果以及青少年大脑认知发展研究（ABCD 研究）和英国生物库（UKB 研究）的个体水平数据，评估了这些六项障碍的预测多基因风险评分（PRS）与观察到的认知功能、行为和脑成像特征之间的相关性。我们进一步研究了大脑结构和功能的中介效应，这些结构和功能在精神分裂症和流体智力之间的遗传风险相关性上存在性别差异。在性别之间，认知特征和精神障碍之间的遗传关联存在显著的异质性。具体来说，男孩的精神分裂症 PRS 与 ABCD 数据集十种认知功能中的八种具有更强的相关性；而女性的自闭症 PRS 与 UKB 数据集中的流体智力具有更强的相关性。除了认知特征，我们还发现精神障碍与行为和脑成像之间的遗传关联存在显著的性别差异。这些结果表明了精神疾病的潜在早期病因，并揭示了性别之间的认知特征和涉及大脑功能的障碍之间存在共同和独特的遗传基础。
