Dataset Information

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank.

ABSTRACT: Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg?=?0.24, p?=?1.8?×?10-7 versus rg?=?-0.05, p?=?0.39 in individuals not reporting trauma exposure, difference p?=?2.3?×?10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

SUBMITTER: Coleman JRI

PROVIDER: S-EPMC7305950 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank.

Coleman Jonathan R I JRI Peyrot Wouter J WJ Purves Kirstin L KL Davis Katrina A S KAS Rayner Christopher C Choi Shing Wan SW Hübel Christopher C Gaspar Héléna A HA Kan Carol C Van der Auwera Sandra S Adams Mark James MJ Lyall Donald M DM Choi Karmel W KW Dunn Erin C EC Vassos Evangelos E Danese Andrea A Maughan Barbara B Grabe Hans J HJ Lewis Cathryn M CM O'Reilly Paul F PF McIntosh Andrew M AM Smith Daniel J DJ Wray Naomi R NR Hotopf Matthew M Eley Thalia C TC Breen Gerome G

Molecular psychiatry 20200123 7

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-repor ...[more]

PMID: 31969693

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Project description:BACKGROUND.:Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD. METHODS.:Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457-14,836, age 45-81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use. RESULTS.:Lifetime MDD was robustly associated with a lower g-factor (? = -0.10, PFDR = 4.7 × 10-5), with impairments in attention, processing speed, and executive functioning (? ? 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (? = -0.18, PFDR = 7.5 × 10-5). CONCLUSIONS.:Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

Dataset Information

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank.

Publications

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank.

Similar Datasets

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