Biological psychiatry · 2026
Polygenic Risk for Major Depression: Diagnostic Specificity and Developmental Trajectories in an Admixed Youth Cohort.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Brañas Marcelo José Abduch Adas, Ito Lucas Toshio, Croci Marcos Signoretti, Ravagnani Salto Ana Beatriz, Doretto Victoria Fogaça, Santoro Marcos Leite, Ota Vanessa Kiyomi, Rohde Luis Augusto, Salum Giovanni Abrahão, Choi-Kain Lois W, Belangero Síntia, Miguel Euripedes Constantino, Hoffmann Maurício Scopel, Pan Pedro Mario
Аннотация
BACKGROUND: Major depressive disorder (MDD) is heritable and polygenic, yet the relative diagnostic specificity, developmental impact, and cross-ancestry generalizability of MDD polygenic risk scores (MDD-PRSs) remain unclear.
METHODS: At 2 sites of the Brazilian High-Risk Cohort (N = 2163; ages 6-23 years; 45.6% female), we used a discovery-replication design to test associations between MDD-PRSs and 1) lifetime DSM-IV diagnoses, 2) longitudinal depressive-symptom trajectories derived from latent growth-curve models, and 3) late-adolescent/young-adult depressive symptoms and nonsuicidal self-injury (NSSI). Analyses used weighted ordinary least squares and quantile regression, adjusting for age, sex, socioeconomic status, genetic principal components, and psychiatric comorbidity.
RESULTS: MDD-PRSs showed relative specificity for MDD in both sites, explaining approximately 2.6% to 3.6% of the liability-scale variance; no other diagnostic category survived false discovery rate correction. Longitudinally, higher MDD-PRSs predicted a higher initial level (β = 0.10-0.18; p < .001 in both sites), a faster rate of increase (β = 0.07-0.10; p = .004 and p < .001), and a higher time-averaged level (β = 0.13-0.20; p < .001 in both sites) of depressive symptoms, with effects strengthening at higher quantiles. Cross-sectionally, MDD-PRSs were associated with more depressive symptoms (β = 0.15-0.17; p < .001 in both sites). For NSSI, a main-effect association was observed (β = 0.09; p < .001), but it remained significant only in a post hoc MDD-PRS × lifetime-MDD interaction among individuals with MDD (β = 0.24; p = .014).
CONCLUSIONS: In this deeply phenotyped, admixed cohort, MDD-PRSs showed relative diagnostic specificity and marked a more severe developmental course of depression, with NSSI associations contingent on MDD diagnosis, supporting the relative specificity, developmental utility, and cross-ancestry relevance of MDD-PRSs.
METHODS: At 2 sites of the Brazilian High-Risk Cohort (N = 2163; ages 6-23 years; 45.6% female), we used a discovery-replication design to test associations between MDD-PRSs and 1) lifetime DSM-IV diagnoses, 2) longitudinal depressive-symptom trajectories derived from latent growth-curve models, and 3) late-adolescent/young-adult depressive symptoms and nonsuicidal self-injury (NSSI). Analyses used weighted ordinary least squares and quantile regression, adjusting for age, sex, socioeconomic status, genetic principal components, and psychiatric comorbidity.
RESULTS: MDD-PRSs showed relative specificity for MDD in both sites, explaining approximately 2.6% to 3.6% of the liability-scale variance; no other diagnostic category survived false discovery rate correction. Longitudinally, higher MDD-PRSs predicted a higher initial level (β = 0.10-0.18; p < .001 in both sites), a faster rate of increase (β = 0.07-0.10; p = .004 and p < .001), and a higher time-averaged level (β = 0.13-0.20; p < .001 in both sites) of depressive symptoms, with effects strengthening at higher quantiles. Cross-sectionally, MDD-PRSs were associated with more depressive symptoms (β = 0.15-0.17; p < .001 in both sites). For NSSI, a main-effect association was observed (β = 0.09; p < .001), but it remained significant only in a post hoc MDD-PRS × lifetime-MDD interaction among individuals with MDD (β = 0.24; p = .014).
CONCLUSIONS: In this deeply phenotyped, admixed cohort, MDD-PRSs showed relative diagnostic specificity and marked a more severe developmental course of depression, with NSSI associations contingent on MDD diagnosis, supporting the relative specificity, developmental utility, and cross-ancestry relevance of MDD-PRSs.