Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition

Adams, M. J. et al. (2020) Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition. Psychological Medicine, 51(15), pp. 2526-2535. (doi: 10.1017/S0033291719002629) (PMID:31576797) (PMCID:PMC7737042)

Abstract

Background: Major depressive disorder and neuroticism (Neu) 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 (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu 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 Neu. Results: We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu 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 Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.

• Item Type: Articles
• Additional Information: This work was supported by Wellcome Trust (A.M.Mc., reference 104036/Z/14/Z) (D.M.H., reference 213674/Z/18/Z), the Medical Research Council (A.M.Mc., reference MC_PC_17209) (I.J.D., reference MR/ K026992/1), Brain & Behavior Research Foundation (D.M.H., reference 27404), the US National Institute of Mental Health (PGC, references 5 U01MH109528-03) and Age UK (W.D.H., reference Disconnected Mind Project).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Daniel
• Authors: Adams, M. J., Howard, D. M., Luciano, M., Clarke, T.-K., Davies, G., Hill, W. D., 23andMe Research Team, , Major Depressive Disorder Working Group of the PGC, , Smith, D., Deary, I. J., Porteous, D. J., and McIntosh, A. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Psychological Medicine
• Publisher: Cambridge University Press
• ISSN: 0033-2917
• ISSN (Online): 1469-8978
• Published Online: 02 October 2019
• Copyright Holders: Copyright © The Authors 2019
• First Published: First published in Psychological Medicine 51(15):2526-2535
• Publisher Policy: Reproduced under a Creative Commons license