# Is there a causal association between temporomandibular disorders and COVID-19 risk? A genetic instrumental variables analysis

## TL;DR

This study investigates whether there is a causal link between temporomandibular disorders and COVID-19 using genetic data, finding no direct causal relationship.

## Contribution

The novelty lies in using bidirectional Mendelian randomization to explore causality between TMD and COVID-19, accounting for confounders.

## Key findings

- No causal effect of TMD on COVID-19 susceptibility was found.
- Reverse analysis showed no significant impact of COVID-19 on TMD.
- Psychological stress from the pandemic may mediate an indirect relationship.

## Abstract

The coronavirus disease 2019 (COVID-19) and
temporomandibular joint disorders (TMD) as the two major
diseases are being focused by the public in modern societies.
Previous epidemiological studies have shown increase in TMD prevalence during
COVID-19 pandemic era. This study was aimed to verify the causal association
between two sides using bidirectional mendelian randomization (MR) analysis. It
explored whether COVID-19 could cause TMD or TMD influenced the COVID-19
susceptibility. Furthermore it was aimed to eliminate the reverse relationship
and other confounders, and an attempt was made to provide etiologic evidence.
Single-nucleotide polymorphisms (SNPs) related to three COVID-19 phenotypes
(p < 5 × 10−8) were selected from the
genome-wide association study (GWAS) data collected through COVID-19 host
genetics initiative (HGI). SNPs related to TMD (p < 5 ×
10−6) were collected from GWAS data in UK Biobank (UKB). Inverse variance
weighted (IVW), weighted median (WM), and MR-Egger regression estimated the
causal effect between two sides in this study. Furthermore, four sensitivity
analyses (MR-PRESSO, Cochran’s Q test, MR-Egger intercept test, and leave-one-out
test) were used to confirm the robust results. TMD-related GWAS in FinnGen
repeated the MR to validate the results. COVID-19 was not affected by TMD. The
reversed MR suggested no significant causal effect of COVID-19 on TMD.
Sensitivity analyses showed no gene pleiotropy and had robust results in this MR.
Nonetheless, the MR statistical power was <80%, which suggested insufficient
sample size of COVID-19 and TMD. This study based on current evidence depicted
that COVID-19 had no impact on TMD, and TMD did not increase the susceptibility
of severe acute respiratory syndrome coronavirus-2. During COVID-19 pandemic,
excessive psychological stress caused by COVID-19 might act as a mediator between
the two diseases. The relationship between the two sides needs verification by
more external studies in the future.