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

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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.

Original languageEnglish
Article number100249
JournalCell Genomics
Volume3
Issue2
ISSN2666-979X
DOIs
Publication statusPublished - Feb 2023

Keywords

  • Mendelian randomization
  • Parkinson's disease
  • blood cell traits
  • blood-based biomarkers
  • genetic correlation
  • neurological and psychiatric disorders
  • platelets

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