The shared genetic landscape of blood cell traits and risk of neurological and psychiatric disorders

Yuanhao Yang; Yuan Zhou; Dale R Nyholt; Chloe X Yap; Rudolph K Tannenberg; Ying Wang; Yang Wu; Zhihong Zhu; Bruce V Taylor; Jacob Gratten

doi:10.1016/j.xgen.2022.100249

The shared genetic landscape of blood cell traits and risk of neurological and psychiatric disorders

Cell Genom. 2023 Jan 25;3(2):100249. doi: 10.1016/j.xgen.2022.100249. eCollection 2023 Feb 8.

Authors

Yuanhao Yang^{1

2}, Yuan Zhou³, Dale R Nyholt⁴, Chloe X Yap^{1

2}, Rudolph K Tannenberg¹, Ying Wang^{5

6

7}, Yang Wu², Zhihong Zhu^{2

8}, Bruce V Taylor³, Jacob Gratten¹

Affiliations

¹ Mater Research Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
² Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
³ Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia.
⁴ School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.
⁵ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
⁶ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁷ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁸ National Centre for Register-based Research, Aarhus University, Aarhus 8210, Denmark.

Abstract

Phenotypic associations have been reported between blood cell traits (BCTs) and a range of neurological and psychiatric disorders (NPDs), but in most cases, it remains unclear whether these associations have a genetic basis and, if so, to what extent genetic correlations reflect causality. Here, we report genetic correlations and Mendelian randomization analyses between 11 NPDs and 29 BCTs, using genome-wide association study summary statistics. We found significant genetic correlations for four BCT-NPD pairs, all of which have prior evidence for a phenotypic correlation. We identified a previously unreported causal effect of increased platelet distribution width on susceptibility to Parkinson's disease. We identified multiple functional genes and regulatory elements for specific BCT-NPD pairs, some of which are targets of known drugs. These results enrich our understanding of the shared genetic landscape underlying BCTs and NPDs and provide a robust foundation for future work to improve prognosis and treatment of common NPDs.

Keywords: Mendelian randomization; Parkinson’s disease; blood cell traits; blood-based biomarkers; genetic correlation; neurological and psychiatric disorders; platelets.

Grants and funding

MC_QA137853/MRC_/Medical Research Council/United Kingdom