Deciphering the Biological Mechanisms Underlying the Genome-Wide Associations between Computerized Device Use and...

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 "weekly usage of mobile phone in last 3 months" (PhoneUse) vs. attention deficit hyperactivity disorder (ADHD; r_g = 0.425, p = 4.59 × 10^-29) and "plays computer games" (CompGaming) vs. schizophrenia (SCZ; r_g = -0.271, p = 7.16 × 10^-26). 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 (PhoneUse→ADHD β = 0.132, p = 1.89 × 10^-4 and ADHD→PhoneUse β = 0.084, p = 2.86 × 10^-10; CompGaming→SCZ β = -0.02, p = 6.46 × 10^-25 and CompGaming→SCZ β = -0.194, p = 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, p = 2.74 × 10^-10) and DRD2 association (p_SCZ = 7.94 × 10^-8; p = 3.98 × 10^-25) were detected in SCZ and CompGaming and support their negative correlative relationship. FOXP2 was significantly associated with ADHD (p = 9.32 × 10^-7) and PhoneUse (p = 9.00 × 10^-11) 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.