Medical comorbidities were assessed by self report using a standard medical questionnaire (Supplementary Data). Selected chronic comorbidities specified a requirement for physician diagnosis, whereas acute or episodic conditions did not. Questionnaires assessing personal and family history of selected infectious, autoimmune, and inflammatory conditions were completed by probands and a subset of the questionnaire was also completed by first-degree relatives (Supplementary Data). These included (1) self-reported history of encephalitis or meningitis, frequent ear/throat infections (frequency not defined), scarlet fever, RF, and rheumatic heart disease in both probands and first-degree relatives; and (2) self-reported physician diagnosis of rheumatoid arthritis (RA), SLE, multiple sclerosis (MS), diabetes, asthma, psoriasis, ulcerative colitis, Crohn's disease, and Sydenham's chorea in probands only. No additional follow-up or verification of reported comorbidities was performed.
