Wendt Frank R, Muniz Carvalho Carolina, Pathak Gita A, Gelernter Joel, Polimanti Renato
Department of Psychiatry, Yale School of Medicine and VA CT Healthcare Center, West Haven, CT 06516, USA.
Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04021-001, Brazil.
J Clin Med. 2019 Nov 21;8(12):2040. doi: 10.3390/jcm8122040.
Computerized device use (CDU) is societally ubiquitous but its effects on mental health are unknown. We performed genetic correlation, Mendelian randomization, and latent causal variable analyses to identify shared genetic mechanisms between psychiatric disorders (Psychiatric Genomics Consortium; 14,477 < N < 150,064) and CDU (UK Biobank; N = 361,194 individuals). Using linkage disequilibrium score regression, we detected strong genetic correlations between " () vs. attention deficit hyperactivity disorder (ADHD; = 0.425, = 4.59 × 10) and " () vs. schizophrenia (SCZ; = -0.271, = 7.16 × 10). Focusing on these correlations, we used two sample MRs to detect the causal relationships between trait pairs by treating single nucleotide polymorphisms as non-modifiable risk factors underlying both phenotypes. Significant bidirectional associations were detected (→ADHD = 0.132, = 1.89 × 10 and ADHD→ = 0.084, = 2.86 × 10; →SCZ = -0.02, = 6.46 × 10 and →SCZ = -0.194, = 0.005) and the latent causal variable analyses did not support a causal relationship independent of the genetic correlations between these traits. This suggests that molecular pathways contribute to the genetic overlap between these traits. Dopamine transport enrichment (Gene Ontology:0015872, = 2.74 × 10) and association ( = 7.94 × 10; = 3.98 × 10) were detected in SCZ and and support their negative correlative relationship. was significantly associated with ADHD ( = 9.32 × 10) and ( = 9.00 × 10) with effect directions concordant with their positive genetic correlation. Our study demonstrates that epidemiological associations between psychiatric disorders and CDUs are due, in part, to the molecular mechanisms shared between them rather than a causal relationship. Our findings imply that biological mechanisms underlying CDU contribute to the psychiatric phenotype manifestation.
计算机化设备使用（CDU）在社会中无处不在，但其对心理健康的影响尚不清楚。我们进行了遗传相关性、孟德尔随机化和潜在因果变量分析，以确定精神疾病（精神基因组学联盟；14477＜N＜150064）和CDU（英国生物银行；N = 361194人）之间共享的遗传机制。使用连锁不平衡评分回归，我们检测到“（）与注意力缺陷多动障碍（ADHD；= 0.425，= 4.59×10）以及“（）与精神分裂症（SCZ；= -0.271，= 7.16×10）之间存在很强的遗传相关性。基于这些相关性，我们使用两样本孟德尔随机化方法，将单核苷酸多态性视为两种表型潜在的不可改变的风险因素，以检测性状对之间的因果关系。检测到显著的双向关联（→ADHD = 0.132，= 1.89×10且ADHD→ = 0.084，= 2.86×10；→SCZ = -0.02，= 6.46×10且→SCZ = -0.194，= 0.005），并且潜在因果变量分析不支持这些性状之间存在独立于遗传相关性的因果关系。这表明分子途径促成了这些性状之间的遗传重叠。在SCZ和（）中检测到多巴胺转运富集（基因本体论：0015872，= 2.74×10）和（）关联（= 7.94ב10；= 3.98×10），并支持它们之间的负相关关系。（）与ADHD显著相关（= 9.32×10），与（）（= 9.00×10）显著相关，效应方向与其正遗传相关性一致。我们的研究表明，精神疾病与CDU之间的流行病学关联部分归因于它们之间共享的分子机制，而非因果关系。我们的研究结果意味着CDU背后的生物学机制促成了精神疾病表型的表现。
