Causality between COVID-19 and multiple myeloma: a two-sample Mendelian randomization study and Bayesian...

Area of Science:

• Genetics
• Epidemiology
• Immunology

Background:

• Infection is a primary cause of illness and death in multiple myeloma (MM) patients.
• Understanding the link between Coronavirus 2019 (COVID-19) and MM is crucial for managing MM patients with COVID-19.
• Previous studies on this relationship were observational and yielded conflicting results.

Purpose of the Study:

• To investigate the causal relationship between COVID-19 infection traits and multiple myeloma using bidirectional Mendelian randomization.
• To identify novel single nucleotide polymorphisms (SNPs) associated with MM through multi-trait analysis of GWAS (MTAG).
• To explore potential biological pathways involved in the COVID-19 and MM association.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis using COVID-19 GWAS data.
• Multi-trait analysis of GWAS (MTAG) to identify new MM-associated SNPs.
• Co-localization and over-representation enrichment analyses to identify causal pathways and biological functions.

Main Results:

• Inverse variance weighted (IVW) analysis indicated that SARS-CoV-2 infection and COVID-19 hospitalization increase MM risk.
• Reverse MR analysis did not find a causal relationship between MM and COVID-19 symptoms.
• Co-localization identified genes (LZTFL1, MUC4, OAS1, HLA-C, SLC22A31, FDX2, MAPT) involved in COVID-19's causal role in MM, primarily related to immune function and viral defense.
• MTAG identified three novel MM-related SNPs potentially regulating B3GNT6 expression.

Conclusions:

• SARS-CoV-2 infection and COVID-19 hospitalization are causally linked to an increased susceptibility to multiple myeloma.
• This study provides the first MR evidence exploring the causality between COVID-19 traits and MM.
• Identified genes and pathways offer insights into the biological mechanisms underlying this association.