White blood cell count associated with genetic predisposition of depression bidirectionally: JAMA

Depression (major depressive disorder) is a common and serious medical illness that negatively affects quality of life however its underlying biological etiology remains poorly understood. Its genetic association is under study and yet to be investigated.

A new study by Julia M. Sealock, BSc and team revealed that increased depression polygenic scores were associated with increased white blood cell count, and suggested that this association might be bidirectional.

Polygenic risk score (PRS) for depression reflects an individual's estimated genetic predisposition for depression and can be used as a predictor for depression.

The findings of the study are published in JAMA Psychiatry.

The objective of the study was to characterize the association between depression polygenic scores and an inflammatory biomarker, ie, white blood cell count.

The study was genetic association study conducted from May 19, 2019, to June 5, 2021, using electronic health record data from 382 452 patients across 4 health care systems. Primary analyses were conducted in Vanderbilt University Medical Center's biobank. Replication analyses were conducted across 3 other PsycheMERGE sites. All patients with available genetic data and recorded white blood cell count measurements were included in the analyses. Primary analyses were conducted in individuals of European descent and then repeated in a population of individuals of African descent.

The results of the study were

• A total of 382 452 participants across the 4 PsycheMERGE sites, there were 18.7% female of European ancestry and 12 383 participants i.e 61.1% female of African ancestry.

• A laboratory-wide association scan revealed a robust association between depression polygenic scores and white blood cell count, which was replicated in a meta-analysis across the 4 health care systems.

• Mediation analyses suggested a bidirectional association, with white blood cell count accounting for 2.5% of the association of depression polygenic score with depression diagnosis and depression diagnosis accounting for 9.8% of the association of depression polygenic score with white blood cell count.

• Mendelian randomization provided additional support for an association between increased white blood count and depression risk, but depression modeled as the exposure showed no evidence of an influence on white blood cell counts.

Sealock and team concluded that "This genetic association study found that increased depression polygenic scores were associated with increased white blood cell count, and suggests that this association may be bidirectional. These findings highlight the potential importance of the immune system in the etiology of depression and may motivate future development of clinical biomarkers and targeted treatment options for depression."

Reference:

Sealock JM, Lee YH, Moscati A, et al. Use of the PsycheMERGE Network to Investigate the Association Between Depression Polygenic Scores and White Blood Cell Count. JAMA Psychiatry. Published online October 20, 2021. doi:10.1001/jamapsychiatry.2021.2959.