Phenome-wide association study identifies new clinical phenotypes associated with Staphylococcus aureus infections

Area of Science:

• Genetics and Genomics
• Epidemiology
• Clinical Informatics

Background:

• Phenome-Wide Association Studies (PheWAS) systematically screen medical records for phenotype associations.
• No prior systematic screening of phenotypes associated with Staphylococcus aureus infections (SAIs) has been conducted.
• Potential novel risk factors and complications of SAIs remain undiscovered.

Purpose of the Study:

• To identify novel phenotypes associated with Staphylococcus aureus infections (SAIs) using a tailored two-stage PheWAS approach.
• To discover new risk factors and complications of SAIs.
• To validate novel associations in independent patient cohorts.

Main Methods:

• A two-stage PheWAS screening procedure was developed.
• Stage one involved screening for co-occurrence of SAIs with other phenotypes.
• Stage two examined age of onset correlations; analysis used Marshfield Clinic Health System data (754,401 patients) and validated findings in TriNetX (109,884,571 patients) and All of Us (118,538 patients) cohorts.

Main Results:

• Forty-one phenotypes met significance criteria (p-value < 3.64e-5, OR > 5).
• Twenty-three associations were classified as risk factors or complications of SAIs.
• Three novel associations were discovered: long-term aspirin use (risk), iron deficiency anemia, and anemia of chronic disease (complications), with replication in validation cohorts.

Conclusions:

• The PheWAS of SAIs enhances understanding of interacting phenotypes.
• The novel two-stage PheWAS methodology can be applied to other disease-disease interaction studies.
• Findings require further investigation due to potential observational data biases.