Associations between major psychiatric disorder polygenic risk scores and blood-based markers in UK Biobank

Sewell, M. D.E. et al. (2021) Associations between major psychiatric disorder polygenic risk scores and blood-based markers in UK Biobank. Brain Behavior and Immunity, 97, pp. 32-41. (doi: 10.1016/j.bbi.2021.06.002) (PMID:34107350)

Abstract

Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors, and are associated with peripheral abnormalities. The relationships between such genetic architectures and blood-based markers are, however, unclear. We investigated relationships between polygenic risk scores (PRS) for these disorders and peripheral markers in the UK Biobank cohort. We calculated polygenic risk scores for n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) UK Biobank cohort subjects. We then examined associations between disorder PRS and 58 inflammatory/immune, hematological, bone, cardiovascular, hormone, liver, renal and diabetes-associated blood markers using two generalized linear regression models: ‘minimally adjusted’ controlling for variables such as age and sex, and ‘fully adjusted’ including additional lifestyle covariates: BMI, alcohol and smoking status, and medication intake. There were 38/58 MDD PRS, 32/58 SCZ PRS, and 20/58 BD PRS-blood marker associations detected for our minimally adjusted model. Of these, 13/38 (MDD PRS), 14/32 (SCZ PRS), and 10/20 (BD PRS) associations remained significant after controlling for lifestyle factors. Many were disorder-specific, with 8/13 unique MDD PRS associations identified. Several disorder-specific associations for MDD and SCZ were immune-related, with mostly positive and negative associations identified for MDD and SCZ PRS respectively. This study suggests that MDD, SCZ and BD have both shared and distinct peripheral markers associated with disorder-specific genetic risk. The results also implicate inflammatory dysfunction in MDD and SCZ, albeit with differences in patterns between the two conditions, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.

• Item Type: Articles
• Additional Information: This study was supported by a Wellcome Trust Strategic Award (“Stratifying Resilience and Depression Longitudinally”; Grant No. 104036/Z/14/Z; principal investigator, AMM). This research was conducted using the UKB Resource under approved project 4844. MDES, LJS, AJES and OMR all receive support from the University of Edinburgh Wellcome Trust Translational Neuroscience 4-year PhD programme (Grant No. 108890/Z/15/Z). CG is supported by The Medical Research Council and The University of Edinburgh through the Precision Medicine Doctoral Training programme.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lyall, Dr Donald
• Authors: Sewell, M. D.E., Jiménez-Sánchez, L., Shen, X., Edmondson-Stait, A. J., Green, C., Adams, M. J., Rifai, O. M., McIntosh, A. M., Lyall, D. M., Whalley, H. C., and Lawrie, S. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: Brain Behavior and Immunity
• Publisher: Elsevier
• ISSN: 0889-1591
• ISSN (Online): 1090-2139
• Published Online: 06 June 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Brain Behavior and Immunity 97: 32-41
• Publisher Policy: Reproduced under a Creative Commons License