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
Affiliations
Yuanhao Yang
Mater Research Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; Corresponding author
Yuan Zhou
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia
Dale R. Nyholt
School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
Chloe X. Yap
Mater Research Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Rudolph K. Tannenberg
Mater Research Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
Ying Wang
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Yang Wu
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Zhihong Zhu
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; National Centre for Register-based Research, Aarhus University, Aarhus 8210, Denmark
Bruce V. Taylor
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia
Jacob Gratten
Mater Research Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia; Corresponding author
Summary: 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.
