Genetic variants associated with platelet count are predictive of human disease and physiological markers

Evgenia Mikaelsdottir,Jon K Sigurdsson,Anna Helgadóttir ,Saedís Saevarsdóttir ,Ólöf Sigurðardóttir ,Sigrún Reykdal ,Kristjan Norland,Thorunn Rafnar,Sigrún H Lund ,Páll T Önundarson ,Ísleifur Ólafsson ,Sölvi Rögnvaldsson ,Ingibjörg Guðmundsdóttir ,Guðmundur Þorgeirsson ,Brynjar Viðarsson ,Guðmar Þorleifsson ,Magnús K Magnússon ,Lilja Stefánsdóttir ,Árni Jón Geirsson ,Gunnar B Ragnarsson,Jūlı́us Guðmundsson ,Gerður Gröndal ,Guðmundur Geirsson ,Vinicius Tragante,Hilma Hólm ,Daníel F Guðbjartsson ,Sigurður Y Kristinsson ,Unnur Þorsteinsdóttir ,Páll Melsted ,Ingileif Jónsdóttir ,Gisli H Halldorsson ,Emil L Sigurðsson ,Kári Stefánsson

doi:10.1038/s42003-021-02642-9

Abstract

Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.

Highlights

Platelets play an important role in hemostasis and other aspects of vascular biology
In the Icelandic study, we analyzed about 32.6 million variants identified through whole-genome sequencing of 28,075 Icelanders and imputed into 139,479 chip-typed individuals and their untyped 1st and 2nd degree relatives[19], or a total of 270,211 individuals with Platelet count (PLT) measurements (“Methods”)
In this study, we identified 577 variants that associate with PLT in the Icelandic and UK populations

Summary

Introduction

Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease. To explore PLT and its connections to diseases and other traits, we conducted a meta-GWAS analysis of PLT using data from 536,974 Europeans from Iceland and the UK and identified 577 independent signals associated with PLT. We assessed genetic sharing by PLT and various diseases and other traits using a PLT polygenic risk score

Methods

Results

Conclusion