KEY TAKEAWAYS
- The PheWAS aimed to investigate the comorbidities associated with OC among older women and identify shared genetic traits.
- Researchers noticed that OC links to digestive and respiratory comorbidities shared genetic variants with diverse diseases and a novel locus tied to skin conditions.
Ovarian cancer (OC) commonly affects older women with comorbidities, prompting a hypothesis-free phenome-wide association study (PheWAS) to uncover associated comorbidities and identify shared genetic traits.
Anwar Mulugeta and the team aimed to access the comprehensive landscape of OC comorbidities and traits with overlapping genetic architectures.
They used data from 181,203 patients and analyzed OC and OC subtype-specific genetic risk scores (GRS) associated with 889 diseases and 43 other traits. Employing PheWAS and colocalization analyses for individual variants, the study aimed to identify evidence for shared genetic architecture.
The OC-GRS associated with 10 diseases exhibited a significant link, while the clear cell OC-GRS demonstrated associations with five diseases at the FDR threshold (P = 5.6 × 10-4). In Mendelian randomization analysis (MR), robust evidence emerged for OC’s association with a higher risk of “secondary malignant neoplasm of digestive systems” (OR 1.64, 95% CI 1.33, 2.02), “ascites” (1.48, 95% CI 1.17, 1.86), “chronic airway obstruction” (1.17, 95% CI 1.07, 1.29), and “abnormal findings on examination of the lung” (1.51, 95% CI 1.22, 1.87). Further support for compromised respiratory function was found in the analysis of lung spirometry measures.
PheWAS on individual OC variants identified 5 genetic variants associated with other diseases and 7 variants associated with biomarkers (all, P ≤ 4.5 × 10-8). Colocalization analysis pinpointed rs4449583 (from TERT locus) as the shared causal variant for OC and seborrheic keratosis.
The study concluded by revealing associations between OC and digestive/respiratory comorbidities. Multiple variants impacting OC risk were linked to various diseases and biomarkers. Additionally, a novel genetic locus shared between OC and skin conditions was identified.
The study is sponsored by the Medical Research Future Fund of Australia
Source: https://pubmed.ncbi.nlm.nih.gov/38457211/
Mulugeta A, Lumsden AL, Madakkatel I, et.al (2024)’’ Phenome-wide association study of ovarian cancer identifies common comorbidities and reveals shared genetics with complex diseases and biomarkers.’’ Cancer Med. 2024 Feb;13(4):e7051. doi: 10.1002/cam4.7051. PMID: 38457211; PMCID: PMC10923028.
