Figure. The comorbidity landscape of patients with tuberous sclerosis complex (TSC).

(A) A Manhattan plot shows the significance level of TSC comorbidities. Common TSC comorbidities, including neoplasms of the brain, kidney, and respiratory organs, autism, epilepsy, developmental delays, and speech and language disorder, have the most significant adjusted p values. A total of 605 phenome-wide association studies (PheWAS) codes showed significant associations with TSC after correcting for multiple testing. (B) Distinct comorbidity patterns were observed in the TSC and non-TSC cohorts between age 0 and 20. Selected comorbidities with the most significant odds ratios (ORs) are shown. Patients with TSC are more likely to develop benign neoplasm of the kidney (OR 2,265.3), malignant neoplasms of the brain (OR 177.2), epilepsy (OR 103.4), and autism (OR 15.7), shown as comorbidity group 1, but less likely to develop infectious mononucleosis (OR 0.410) and perinatal jaundice (OR 0.720), shown as comorbidity group 2. PheWAS codes and descriptions were shown.