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<p>The genetic risk of persistent distressing psychotic-like experiences (PLE) in the multiancestral population is underinvestigated. The gene–neighborhood environment interaction in persistent distressing PLE is also unknown. This study included 6,449 participants from the Adolescent Brain and Cognitive Development Study. The genetic risk was measured by a multiancestral schizophrenia polygenic risk score (SCZ-PRS). The multidimensional neighborhood-level exposures were used to form the neighborhood exposome (NE). SCZ-PRS was not statistically significantly associated with odds of persistent distressing PLE (odds ratio (OR) of 1.04, 95% confidence intervals (CI) 0.97 to 1.13, <i>P</i> = 0.280), whereas the NE score was (OR of 1.15, 95% CI 1.05 to 1.26, <i>P</i> = 0.003). A significant negative multiplicative interaction between SCZ-PRS and NE was found (estimate of −0.08, 95% CI −0.15 to −0.00, <i>P</i> = 0.039). The additive interaction followed the same direction but was statistically insignificant (estimate of −0.06, 95% CI −0.15 to 0.03, <i>P</i> = 0.189). Persistent distressing PLE in children may be driven by detrimental neighborhood exposures in multiancestral populations, particularly among those with low genetic risk. Here the findings provide important evidence on persistent distressing PLE etiology attributed to genetic and environmental risks and identify potential susceptible populations for targeted interventions.</p>

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Interaction between neighborhood exposome and genetic risk in persistent distressing psychotic-like experiences in children

  • 期刊论文

  • 发表日期：

    2026年1月2日

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  • Yinxian Chen,
  • Qingyue Yuan,
  • Lina Dimitrov,
  • Benjamin Risk,
  • Benson Ku,
  • Anke Hüls

摘要

The genetic risk of persistent distressing psychotic-like experiences (PLE) in the multiancestral population is underinvestigated. The gene–neighborhood environment interaction in persistent distressing PLE is also unknown. This study included 6,449 participants from the Adolescent Brain and Cognitive Development Study. The genetic risk was measured by a multiancestral schizophrenia polygenic risk score (SCZ-PRS). The multidimensional neighborhood-level exposures were used to form the neighborhood exposome (NE). SCZ-PRS was not statistically significantly associated with odds of persistent distressing PLE (odds ratio (OR) of 1.04, 95% confidence intervals (CI) 0.97 to 1.13, P = 0.280), whereas the NE score was (OR of 1.15, 95% CI 1.05 to 1.26, P = 0.003). A significant negative multiplicative interaction between SCZ-PRS and NE was found (estimate of −0.08, 95% CI −0.15 to −0.00, P = 0.039). The additive interaction followed the same direction but was statistically insignificant (estimate of −0.06, 95% CI −0.15 to 0.03, P = 0.189). Persistent distressing PLE in children may be driven by detrimental neighborhood exposures in multiancestral populations, particularly among those with low genetic risk. Here the findings provide important evidence on persistent distressing PLE etiology attributed to genetic and environmental risks and identify potential susceptible populations for targeted interventions.