Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US
Abstract There has recently been marked progress in identifying genetic risk factors for major depression (MD) and bipolar disorder (BD); however, few systematic efforts have been made to elucidate heterogeneity that exists within and across these diagnostic taxa. The Affective disorders, Environmen...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-03-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-01877-2 |
| _version_ | 1819177032164048896 |
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| author | Maria Dalby Morana Vitezic Niels Plath Lene Hammer-Helmich Yunxuan Jiang Chao Tian Devika Dhamija Catherine H. Wilson David Hinds 23andMe Research Team Patrick F. Sullivan Joshua W. Buckholtz Jordan W. Smoller |
| author_facet | Maria Dalby Morana Vitezic Niels Plath Lene Hammer-Helmich Yunxuan Jiang Chao Tian Devika Dhamija Catherine H. Wilson David Hinds 23andMe Research Team Patrick F. Sullivan Joshua W. Buckholtz Jordan W. Smoller |
| author_sort | Maria Dalby |
| collection | DOAJ |
| description | Abstract There has recently been marked progress in identifying genetic risk factors for major depression (MD) and bipolar disorder (BD); however, few systematic efforts have been made to elucidate heterogeneity that exists within and across these diagnostic taxa. The Affective disorders, Environment, and Cognitive Trait (AFFECT) study presents an opportunity to identify and associate the structure of cognition and symptom-level domains across the mood disorder spectrum in a prospective study from a diverse US population. Participants were recruited from the 23andMe, Inc research participant database and through social media; self-reported diagnosis of MD or BD by a medical professional and medication status data were used to enrich for mood-disorder cases. Remote assessments were used to acquire an extensive range of phenotypes, including mood state, transdiagnostic symptom severity, task-based measures of cognition, environmental exposures, personality traits. In this paper we describe the study design, and the demographic and clinical characteristics of the cohort. In addition we report genetic ancestry, SNP heritability, and genetic correlations with other large cohorts of mood disorders. A total of 48,467 participants were enrolled: 14,768 with MD, 9864 with BD, and 23,835 controls. Upon enrollment, 47% of participants with MD and 27% with BD indicated being in an active mood episode. Cases reported early ages of onset (mean = 13.2 and 14.3 years for MD and BD, respectively), and high levels of recurrence (78.6% and 84.9% with >5 episodes), psychotherapy, and psychotropic medication use. SNP heritability on the liability scale for the ascertained MD participants (0.19–0.21) was consistent with the high level of disease severity in this cohort, while BD heritability estimates (0.16–0.22) were comparable to reports in other large scale genomic studies of mood disorders. Genetic correlations between the AFFECT cohort and other large-scale cohorts were high for MD but not for BD. By incorporating transdiagnostic symptom assessments, repeated measures, and genomic data, the AFFECT study represents a unique resource for dissecting the structure of mood disorders across multiple levels of analysis. In addition, the fully remote nature of the study provides valuable insights for future virtual and decentralized clinical trials within mood disorders. |
| first_indexed | 2024-12-22T21:20:12Z |
| format | Article |
| id | doaj.art-2934a1ae4c9b4c3390d3ef222727881c |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-22T21:20:12Z |
| publishDate | 2022-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-2934a1ae4c9b4c3390d3ef222727881c2022-12-21T18:12:13ZengNature Publishing GroupTranslational Psychiatry2158-31882022-03-0112111010.1038/s41398-022-01877-2Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the USMaria Dalby0Morana Vitezic1Niels Plath2Lene Hammer-Helmich3Yunxuan Jiang4Chao Tian5Devika Dhamija6Catherine H. Wilson7David Hinds823andMe Research TeamPatrick F. Sullivan9Joshua W. Buckholtz10Jordan W. Smoller11H. Lundbeck A/SH. Lundbeck A/SH. Lundbeck A/SH. Lundbeck A/S23andMe Inc23andMe Inc23andMe Inc23andMe Inc23andMe IncDepartment of Medical Epidemiology and Biostatistics, Karolinska InstituteteDepartment of Psychology, Harvard UniversityStanley Center for Psychiatric Research, Broad Institute of MIT and HarvardAbstract There has recently been marked progress in identifying genetic risk factors for major depression (MD) and bipolar disorder (BD); however, few systematic efforts have been made to elucidate heterogeneity that exists within and across these diagnostic taxa. The Affective disorders, Environment, and Cognitive Trait (AFFECT) study presents an opportunity to identify and associate the structure of cognition and symptom-level domains across the mood disorder spectrum in a prospective study from a diverse US population. Participants were recruited from the 23andMe, Inc research participant database and through social media; self-reported diagnosis of MD or BD by a medical professional and medication status data were used to enrich for mood-disorder cases. Remote assessments were used to acquire an extensive range of phenotypes, including mood state, transdiagnostic symptom severity, task-based measures of cognition, environmental exposures, personality traits. In this paper we describe the study design, and the demographic and clinical characteristics of the cohort. In addition we report genetic ancestry, SNP heritability, and genetic correlations with other large cohorts of mood disorders. A total of 48,467 participants were enrolled: 14,768 with MD, 9864 with BD, and 23,835 controls. Upon enrollment, 47% of participants with MD and 27% with BD indicated being in an active mood episode. Cases reported early ages of onset (mean = 13.2 and 14.3 years for MD and BD, respectively), and high levels of recurrence (78.6% and 84.9% with >5 episodes), psychotherapy, and psychotropic medication use. SNP heritability on the liability scale for the ascertained MD participants (0.19–0.21) was consistent with the high level of disease severity in this cohort, while BD heritability estimates (0.16–0.22) were comparable to reports in other large scale genomic studies of mood disorders. Genetic correlations between the AFFECT cohort and other large-scale cohorts were high for MD but not for BD. By incorporating transdiagnostic symptom assessments, repeated measures, and genomic data, the AFFECT study represents a unique resource for dissecting the structure of mood disorders across multiple levels of analysis. In addition, the fully remote nature of the study provides valuable insights for future virtual and decentralized clinical trials within mood disorders.https://doi.org/10.1038/s41398-022-01877-2 |
| spellingShingle | Maria Dalby Morana Vitezic Niels Plath Lene Hammer-Helmich Yunxuan Jiang Chao Tian Devika Dhamija Catherine H. Wilson David Hinds 23andMe Research Team Patrick F. Sullivan Joshua W. Buckholtz Jordan W. Smoller Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US Translational Psychiatry |
| title | Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US |
| title_full | Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US |
| title_fullStr | Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US |
| title_full_unstemmed | Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US |
| title_short | Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US |
| title_sort | characterizing mood disorders in the affect study a large longitudinal and phenotypically rich genetic cohort in the us |
| url | https://doi.org/10.1038/s41398-022-01877-2 |
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