DRD2 and FOXP2 are implicated in the associations between computerized device use and psychiatric disorders

Abstract

The societal health effects of ubiquitous computerized device use (CDU) is mostly unknown.Epidemiological evidence supports associations between CDU and psychiatric traits, but the underlying biological mechanisms are unclear. We investigated genetic overlaps, causal relationships, and molecular pathways shared between these traits using genome-wide data regarding CDU (UK Biobank; up to N=361,194 individuals) and Psychiatric Genomics Consortium phenotypes (14,477<N<150,064). The strongest genetic correlations were between "weekly usage of mobile phone in last 3 months" (PhoneUse) vs. attention deficit hyperactivity disorder (ADHD) (rg=0.425, p=4.59x10 -11 ) and "plays computer games" (CompGaming) vs. schizophrenia (SCZ) (rg=-0.271, p=7.16x10 -26 ). Latent causal variable analysis did not support causal relationships between these traits, but the observed genetic overlap was related to shared molecular pathways, including: dopamine transport (Gene Ontology:0015872, pSCZvsCompGaming=2.74x10 -10 ) and DRD2 association (pSCZ=7.94x10 -8 ; pCompGaming=3.98x10 -25 ), and FOXP2 association (pADHD=9.32x10 -7 ; pPhoneUse=9.00x10 -11 ). Our results support epidemiological observations with genetic data, and uncover biological mechanisms underlying psychiatric disorders contribution to CDUs.

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

“…To assess causality among MD, AD, AC-quantity, and AC-frequency, we used GWAS summary association data to conduct two-sample MR analyses (Davey Smith and Hemani, 2014; Burgess et al ., 2015). Since different MR methods have sensitivities to different potential issues, accommodate different scenarios, and vary in their statistical efficiency (Polimanti et al ., 2017, 2018; Ravera et al ., 2018; Wendt et al ., 2018), we considered multiple MR methods (online Supplemental Table S1). These include methods based on median (Bowden et al ., 2017), mean (Bowden et al ., 2016), and mode (Hartwig et al ., 2017), and various adjustments, such as fixed v .…”

Economic status mediates the relationship between educational attainment and posttraumatic stress disorder: a multivariable Mendelian randomization study

“…Large scale genome-wide association studies (GWAS) have now identified genetic variants that can be used to define reliable genetic instruments that can be applied for causal inference in a MR analysis. [14][15][16][17][18] The basic principle in MR is that genetic variants that either alter the level of, or mirror the biological effects of, a modifiable environmental exposure that itself alters disease risk should be related to disease risk to the extent predicted by their influence on exposure to the environmental risk factor. 19 Previous large-scale GWAS conducted by the Social Science Genetic Association Consortium (SSGAC) investigated traits related to educational attainment (e.g., number of years of schooling and most advanced math course ever successfully completed), identifying a number of loci and biological pathways regulating brain mechanisms at the basis of the human cognitive ability.…”

A Genome-wide Association Study Identifies Novel Genetic Variants Associated with Neck or Shoulder Pain in the UK Biobank (N = 441,757)

“…In a previous GWAS analysis, FOXP2 has been confirmed to be associated with neck or shoulder pain, and multi-site chronic pain (Johnston et al 2019; Meng et al 2020). In addition, FOXP2 has been found to be associated with the development of attention deficit hyperactivity disorder and psychological disorders (Wendt et al 2018; Meyer et al 2023). The identified brain regions, including the hypothalamus, are known to play crucial roles in central neuroendocrine and hormone secretion (Markakis 2002).…”