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Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition

Adams, M., Howard, D., Luciano, M., Clarke, T., Davies, G., Hill, W.D., Major Depressive Disorder Working Group of the PG, , Jones, Lisa, Smith, D., Deary, I., Porteous, D. and McIntosh, A. (2019) Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition. Psychological Medicine. ISSN Print: 0033-2917 Online: 1469-8978 (In Press)

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Abstract

Background. Major depressive disorder and neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. Methods. We analysed summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium, 23andMe, and UK Biobank) and compared them to genome-wide association studies (GWAS) of neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with neuroticism. Results. We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with neuroticism. The overlapping common genetic variance of depression and neuroticism was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that was not shared with neuroticism, was positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with neuroticism, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease, and age of first birth. Independent of depression, neuroticism had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia, and education. Conclusion. Our findings demonstrate that, while genetic risk factors for depression are largely shared with neuroticism, there are also non-neuroticism related features of depression that may be useful for further patient or phenotypic stratification.

Item Type: Article
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The full-text of the online published article can be accessed via the official URL.

© The Author(s) 2019. This is an Open Access
article, distributed under the terms of the
Creative Commons Attribution licence (http://
creativecommons.org/licenses/by/4.0/), which
permits unrestricted re-use, distribution, and
reproduction in any medium, provided the
original work is properly cited.

The full-text of the online published article can be accessed via the official URL.

Uncontrolled Keywords: diagnosis, genetic correlation, genome-wide association study, major depressive disorder, neuroticism
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Divisions (2019 onwards) > College of Health, Life and Environmental Sciences > School of Allied Health and Community
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Copyright Info: Open access article
Depositing User: Katherine Gordon-Smith
Date Deposited: 18 Oct 2019 12:26
Last Modified: 18 Oct 2019 12:26
URI: https://eprints.worc.ac.uk/id/eprint/8783

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