Cohort profile: the Australian genetics of depression study

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Abstract

Purpose

Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants.

Participants

A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail.

Findings to date

95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed.

Future plans

A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned.

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Most cited references 12

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Exploring Comorbidity Within Mental Disorders Among a Danish National Population

Oleguer Plana-Ripoll, Carsten Pedersen, Yan Holtz … (2019)

Importance Individuals with mental disorders often develop comorbidity over time. Past studies of comorbidity have often restricted analyses to a subset of disorders and few studies have provided absolute risks of later comorbidity. Objectives To undertake a comprehensive study of comorbidity within mental disorders, by providing temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and to develop an interactive website to visualize all results and guide future research and clinical practice. Design, Setting, and Participants This population-based cohort study included all individuals born in Denmark between January 1, 1900, and December 31, 2015, and living in the country between January 1, 2000, and December 31, 2016. The analyses were conducted between June 2017 and May 2018. Main Outcomes and Measures Danish health registers were used to identify mental disorders, which were examined within the broad 10-level International Statistical Classification of Diseases and Related Health Problems, 10th Revision , subchapter groups (eg, codes F00-F09 and F10-F19). For each temporally ordered pair of disorders, overall and lagged hazard ratios and 95% CIs were calculated using Cox proportional hazards regression models. Absolute risks were estimated using competing risks survival analyses. Estimates for each sex were generated. Results A total of 5 940 778 persons were included in this study (2 958 293 men and 2 982 485 women; mean [SD] age at beginning of follow-up, 32.1 [25.4] years). They were followed up for 83.9 million person-years. All mental disorders were associated with an increased risk of all other mental disorders when adjusting for sex, age, and calendar time (hazard ratios ranging from 2.0 [95% CI, 1.7-2.4] for prior intellectual disabilities and later eating disorders to 48.6 [95% CI, 46.6-50.7] for prior developmental disorders and later intellectual disabilities). The hazard ratios were temporally patterned, with higher estimates during the first year after the onset of the first disorder, but with persistently elevated rates during the entire observation period. Some disorders were associated with substantial absolute risks of developing specific later disorders (eg, 30.6% [95% CI, 29.3%-32.0%] of men and 38.4% [95% CI, 37.5%-39.4%] of women with a diagnosis of mood disorders before age 20 years developed neurotic disorders within the following 5 years). Conclusions and Relevance Comorbidity within mental disorders is pervasive, and the risk persists over time. This study provides disorder-, sex-, and age-specific relative and absolute risks of the comorbidity of mental disorders. Web-based interactive data visualization tools are provided for clinical utility. This population-based cohort study examines comorbidity within mental disorders, provides temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and develops an interactive website to visualize all results and guide future research and clinical practice. Question After an individual receives a diagnosis of a specific mental disorder, does the risk of developing other mental disorders increase? Findings This population-based cohort study of 5 940 778 individuals, followed up for 83.9 million person-years, found that comorbidity within mental disorders was pervasive (there was an increased risk of developing all other mental disorders after an index mental disorder) and that the risk of developing comorbidity was most prominent in the first year after the onset of a mental disorder; however, the increased risk persisted over at least 15 years. For some disorders (eg, mood disorders) the absolute risks of developing specific later disorders (eg, anxiety disorders) was substantial (eg, 30%-40% over 5 years). Meaning If clinicians and individuals with mental disorders had ready access to diagnosis-, age-, and sex-specific absolute risks of potential future comorbidity, this information could permit more tailored interventions and better education about self-management (ie, personalized medicine).

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Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children

Amy E Taylor, Hannah J Jones, Hannah Sallis … (2018)

Abstract Background It is often assumed that selection (including participation and dropout) does not represent an important source of bias in genetic studies. However, there is little evidence to date on the effect of genetic factors on participation. Methods Using data on mothers (N = 7486) and children (N = 7508) from the Avon Longitudinal Study of Parents and Children, we: (i) examined the association of polygenic risk scores for a range of sociodemographic and lifestyle characteristics and health conditions related to continued participation; (ii) investigated whether associations of polygenic scores with body mass index (BMI; derived from self-reported weight and height) and self-reported smoking differed in the largest sample with genetic data and a subsample who participated in a recent follow-up; and (iii) determined the proportion of variation in participation explained by common genetic variants, using genome-wide data. Results We found evidence that polygenic scores for higher education, agreeableness and openness were associated with higher participation; and polygenic scores for smoking initiation, higher BMI, neuroticism, schizophrenia, attention-deficit hyperactivity disorder (ADHD) and depression were associated with lower participation. Associations between the polygenic score for education and self-reported smoking differed between the largest sample with genetic data [odds ratio (OR) for ever smoking per standard deviation (SD) increase in polygenic score: 0.85, 95% confidence interval (CI): 0.81, 0.89} and subsample (OR: 0.96, 95% CI: 0.89, 1.03). In genome-wide analysis, single nucleotide polymorphism based heritability explained 18–32% of variability in participation. Conclusions Genetic association studies, including Mendelian randomization, can be biased by selection, including loss to follow-up. Genetic risk for dropout should be considered in all analyses of studies with selective participation.

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Contribution of common genetic variants to antidepressant response.

Rudolf Uher, Jens Wendland, Peter McGuffin … (2013)

Pharmacogenetic studies aiming to personalize the treatment of depression are based on the assumption that response to antidepressants is a heritable trait, but there is no compelling evidence to support this. We estimate the contribution of common genetic variation to antidepressant response with Genome-Wide Complex Trait Analysis in a combined sample of 2799 antidepressant-treated subjects with major depressive disorder and genome-wide genotype data. We find that common genetic variants explain 42% (SE = .180, p = .009) of individual differences in antidepressant response. These results suggest that response to antidepressants is a complex trait with substantial contribution from a large number of common genetic variants of small effect. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2020

Publication date (Electronic): 26 May 2020

Volume: 10

Issue: 5

Electronic Location Identifier: e032580

Affiliations

[1 ]departmentInstitute for Molecular Bioscience , University of Queensland , Brisbane, Queensland, Australia

[2 ]QIMR Berghofer Medical Research Institute , Herston, Queensland, Australia

[3 ]departmentQueensland Brain Institute , The University of Queensland , Brisbane, Queensland, Australia

[4 ]Queensland Centre for Mental Health Research , Wacol, QLD, Australia

[5 ]departmentNational Center for Register-based Research , University of Aarhus , Aarhus, Denmark

[6 ]departmentSchool of Health and Life Sciences , Federation University , Ballarat, Victoria, Australia

[7 ]departmentDepartment of Psychiatry and Behavioural Sciences , Stanford University , Stanford, California, USA

[8 ]departmentDepartment of Psychiatry , State University of New York Upstate Medical University , Syracuse, New York, USA

[9 ]departmentCollege of Medicine , State University of New York Upstate Medical University , Syracuse, NY, United States

[10 ]departmentBrain and Mind Centre , The University of Sydney , Sydney, New South Wales, Australia

Author notes

[Correspondence to ] Dr Enda M Byrne; enda.byrne@ 123456uq.edu.au

Author information

Enda M Byrne http://orcid.org/0000-0002-9491-7797

Article

Publisher ID: bmjopen-2019-032580

DOI: 10.1136/bmjopen-2019-032580

PMC ID: 7259831

PubMed ID: 32461290

SO-VID: 4506938c-476f-44c2-9577-e9ed08c5a8e1

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 27 June 2019

Date revision received : 23 March 2020

Date accepted : 15 April 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;

Award ID: 1086683

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ScienceOpen disciplines: Medicine

Keywords: depression & mood disorders,genetics,anxiety disorders

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ScienceOpen disciplines: Medicine

Keywords: depression & mood disorders, genetics, anxiety disorders

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Cohort profile: the Australian genetics of depression study

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Abstract

Purpose

Participants

Findings to date

Future plans

Related collections

Measurement of Glucocorticoid Receptor Signaling in Major Depression

Most cited references 12

Exploring Comorbidity Within Mental Disorders Among a Danish National Population

Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children

Contribution of common genetic variants to antidepressant response.

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Cited by 27

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