Jai L Shah1,2, Sinan Guloksuz3,4, Vincent Paquin1,2, Lotta-Katrin Pries5, Margreet Ten Have6, Maarten Bak5,7, Nicole Gunther5,8, Ron de Graaf6, Saskia van Dorsselaer6, Bochao D Lin5,9,10, Kristel R van Eijk11, Gunter Kenis5, Alexander Richards12, Michael C O'Donovan12, Jurjen J Luykx5,9,10,13, Bart P F Rutten5, Jim van Os5,6,9,10,14. 1. Prevention and Early Intervention Program for Psychosis (PEPP-Montreal), Douglas Mental Health University Institute, Montreal, QC, Canada. 2. Department of Psychiatry, McGill University, Montreal, QC, Canada. 3. Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University Medical Centre, Vijverdalseweg 1, SN.2.068, P.O.Box 616 6200, Maastricht, MD, The Netherlands. sinan.guloksuz@maastrichtuniversity.nl. 4. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. sinan.guloksuz@maastrichtuniversity.nl. 5. Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University Medical Centre, Vijverdalseweg 1, SN.2.068, P.O.Box 616 6200, Maastricht, MD, The Netherlands. 6. Department of Epidemiology, Netherlands Institute of Mental Health and Addiction, Utrecht, The Netherlands. 7. FACT, Mondriaan Mental Health, Maastricht, The Netherlands. 8. School of Psychology, Open University, Heerlen, The Netherlands. 9. Department of Psychiatry, UMC Utrecht Brain Center, University Medical Centre Utrecht, Utrecht, The Netherlands. 10. Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, The Netherlands. 11. Department of Neurology, UMC Utrecht Brain Center, University Medical Centre Utrecht, Utrecht, The Netherlands. 12. Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK. 13. GGNet Mental Health, Warnsveld, The Netherlands. 14. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
Abstract
PURPOSE: The health correlates of polygenic risk (PRS-SCZ) and exposome (ES-SCZ) scores for schizophrenia may vary depending on age and sex. We aimed to examine age- and sex-specific associations of PRS-SCZ and ES-SCZ with self-reported health in the general population. METHODS: Participants were from the population-based Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Mental and physical health were measured with the 36-item Short Form Survey 4 times between 2007 and 2018. The PRS-SCZ and ES-SCZ were respectively calculated from common genetic variants and exposures (cannabis use, winter birth, hearing impairment, and five childhood adversity categories). Moderation by age and sex was examined in linear mixed models. RESULTS: For PRS-SCZ and ES-SCZ analyses, we included 3099 and 6264 participants, respectively (age range 18-65 years; 55.7-56.1% female). Age and sex did not interact with PRS-SCZ. Age moderated the association between ES-SCZ and mental (interaction: p = 0.02) and physical health (p = 0.0007): at age 18, + 1.00 of ES-SCZ was associated with - 0.10 of mental health and - 0.08 of physical health, whereas at age 65, it was associated with - 0.21 and - 0.23, respectively (all units in standard deviations). Sex moderated the association between ES-SCZ and physical health (p < .0001): + 1.00 of ES-SCZ was associated with - 0.19 of physical health among female and - 0.11 among male individuals. CONCLUSION: There were larger associations between higher ES-SCZ and poorer health among female and older individuals. Accounting for these interactions may increase ES-SCZ precision and help uncover populational determinants of environmental influences on health.
PURPOSE: The health correlates of polygenic risk (PRS-SCZ) and exposome (ES-SCZ) scores for schizophrenia may vary depending on age and sex. We aimed to examine age- and sex-specific associations of PRS-SCZ and ES-SCZ with self-reported health in the general population. METHODS: Participants were from the population-based Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Mental and physical health were measured with the 36-item Short Form Survey 4 times between 2007 and 2018. The PRS-SCZ and ES-SCZ were respectively calculated from common genetic variants and exposures (cannabis use, winter birth, hearing impairment, and five childhood adversity categories). Moderation by age and sex was examined in linear mixed models. RESULTS: For PRS-SCZ and ES-SCZ analyses, we included 3099 and 6264 participants, respectively (age range 18-65 years; 55.7-56.1% female). Age and sex did not interact with PRS-SCZ. Age moderated the association between ES-SCZ and mental (interaction: p = 0.02) and physical health (p = 0.0007): at age 18, + 1.00 of ES-SCZ was associated with - 0.10 of mental health and - 0.08 of physical health, whereas at age 65, it was associated with - 0.21 and - 0.23, respectively (all units in standard deviations). Sex moderated the association between ES-SCZ and physical health (p < .0001): + 1.00 of ES-SCZ was associated with - 0.19 of physical health among female and - 0.11 among male individuals. CONCLUSION: There were larger associations between higher ES-SCZ and poorer health among female and older individuals. Accounting for these interactions may increase ES-SCZ precision and help uncover populational determinants of environmental influences on health.
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