Exploring the genetic heterogeneity in major depression across diagnostic criteria
| العنوان: | Exploring the genetic heterogeneity in major depression across diagnostic criteria |
|---|---|
| المؤلفون: | Cathryn M. Lewis, Bradley Jermy, Jonathan R. I. Coleman, Evangelos Vassos, Kylie P. Glanville |
| المصدر: | Molecular Psychiatry. 26:7337-7345 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Persistence (psychology), Genetic heterogeneity, Anhedonia, Heritability, Biology, medicine.disease, 03 medical and health sciences, Cellular and Molecular Neuroscience, Psychiatry and Mental health, 030104 developmental biology, 0302 clinical medicine, medicine, Etiology, SNP, Major depressive disorder, medicine.symptom, Molecular Biology, 030217 neurology & neurosurgery, Depression (differential diagnoses), Demography |
| الوصف: | Major depressive disorder (MDD) is defined differently across genetic research studies and this may be a key source of heterogeneity. While previous literature highlights differences between minimal and strict phenotypes, the components contributing to this heterogeneity have not been identified. Using the cardinal symptoms (depressed mood/anhedonia) as a baseline, we build MDD phenotypes using five components—(1) five or more symptoms, (2) episode duration, (3) functional impairment, (4) episode persistence, and (5) episode recurrence—to determine the contributors to such heterogeneity. Thirty-two depression phenotypes which systematically incorporate different combinations of MDD components were created using the mental health questionnaire data within the UK Biobank. SNP-based heritabilities and genetic correlations with three previously defined major depression phenotypes were calculated (Psychiatric Genomics Consortium (PGC) defined depression, 23andMe self-reported depression and broad depression) and differences between estimates analysed. All phenotypes were heritable (h2SNP range: 0.102–0.162) and showed substantial genetic correlations with other major depression phenotypes (Rg range: 0.651–0.895 (PGC); 0.652–0.837 (23andMe); 0.699–0.900 (broad depression)). The strongest effect on SNP-based heritability was from the requirement for five or more symptoms (1.4% average increase) and for a long episode duration (2.7% average decrease). No significant differences were noted between genetic correlations. While there is some variation, the two cardinal symptoms largely reflect the genetic aetiology of phenotypes incorporating more MDD components. These components may index severity, however, their impact on heterogeneity in genetic results is likely to be limited. |
| تدمد: | 1476-5578 1359-4184 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::9627dd5c6fc07856fce53cba590e1fc8Test https://doi.org/10.1038/s41380-021-01231-wTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........9627dd5c6fc07856fce53cba590e1fc8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765578 13594184 |
|---|