Kelli Lehto1, Sara Hägg2, Donghao Lu3, Robert Karlsson2, Nancy L Pedersen2, Miriam A Mosing4. 1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Chronic Diseases, National Institute for Health Development, Talinn, Estonia. Electronic address: kelli.lehto@ki.se. 2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND: Being adopted early in life, an indicator of exposure to early-life adversity, has been consistently associated with poor mental health outcomes in adulthood. Such associations have largely been attributed to stressful environments, e.g., exposure to trauma, abuse, or neglect. However, mental health is substantially heritable, and genetic influences may contribute to the exposure to childhood adversity, resulting in potential genetic confounding of such associations. METHODS: Here, we explored associations between childhood adoption and mental health-related outcomes in midlife in 243,797 UK Biobank participants (n adopted = 3151). We used linkage disequilibrium score regression and polygenic risk scores for depressive symptoms, schizophrenia, neuroticism, and subjective well-being to address potential genetic confounding (gene-environment correlations) and gene-environment interactions. As outcomes, we explored depressive symptoms, bipolar disorder, neuroticism, loneliness, and mental health-related socioeconomic and psychosocial measures in adoptees compared with nonadopted participants. RESULTS: Adoptees were slightly worse off on almost all mental, socioeconomic, and psychosocial measures. Each standard deviation increase in polygenic risk for depressive symptoms, schizophrenia, and neuroticism was associated with 6%, 5%, and 6% increase in the odds of being adopted, respectively. Significant genetic correlations between adoption status and depressive symptoms, major depression, and schizophrenia were observed. No evidence for gene-environment interaction between genetic risk and adoption on mental health was found. CONCLUSIONS: The association between childhood adoption and mental health cannot fully be attributed to stressful environments but is partly explained by differences in genetic risk between adoptees and those who have not been adopted (i.e., gene-environment correlation).
BACKGROUND: Being adopted early in life, an indicator of exposure to early-life adversity, has been consistently associated with poor mental health outcomes in adulthood. Such associations have largely been attributed to stressful environments, e.g., exposure to trauma, abuse, or neglect. However, mental health is substantially heritable, and genetic influences may contribute to the exposure to childhood adversity, resulting in potential genetic confounding of such associations. METHODS: Here, we explored associations between childhood adoption and mental health-related outcomes in midlife in 243,797 UK Biobank participants (n adopted = 3151). We used linkage disequilibrium score regression and polygenic risk scores for depressive symptoms, schizophrenia, neuroticism, and subjective well-being to address potential genetic confounding (gene-environment correlations) and gene-environment interactions. As outcomes, we explored depressive symptoms, bipolar disorder, neuroticism, loneliness, and mental health-related socioeconomic and psychosocial measures in adoptees compared with nonadopted participants. RESULTS: Adoptees were slightly worse off on almost all mental, socioeconomic, and psychosocial measures. Each standard deviation increase in polygenic risk for depressive symptoms, schizophrenia, and neuroticism was associated with 6%, 5%, and 6% increase in the odds of being adopted, respectively. Significant genetic correlations between adoption status and depressive symptoms, major depression, and schizophrenia were observed. No evidence for gene-environment interaction between genetic risk and adoption on mental health was found. CONCLUSIONS: The association between childhood adoption and mental health cannot fully be attributed to stressful environments but is partly explained by differences in genetic risk between adoptees and those who have not been adopted (i.e., gene-environment correlation).
Authors: Grace E Woolway; Sophie E Smart; Amy J Lynham; Jennifer L Lloyd; Michael J Owen; Ian R Jones; James T R Walters; Sophie E Legge Journal: Schizophr Bull Date: 2022-09-01 Impact factor: 7.348
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