Northwestern European Ancestry Predominates in Idiopathic Subglottic Stenosis: Results From an English-Speaking...

To investigate the ancestral background of patients with idiopathic subglottic stenosis (iSGS) using genetic testing results.

A de-identified survey collecting genetic testing service ancestry data results, in addition to self-reported ancestry, personal autoimmune history, and any family history of iSGS, was distributed to members of the Facebook group "Living with Idiopathic Subglottic Stenosis." Exclusion criteria included age < 18, non-idiopathic stenosis or ANCA-positive antibody status, and supraglottic or tracheobronchial location of stenosis.

A total of 1242 participants (99.4% female) met inclusion criteria, with 62.4% residing in the US. Genetic testing service results were available in 377 patients, in which European ancestry was most reported (86.6%), specifically Northwestern Europe. By country, ancestry within the United Kingdom, Ireland, and Germany were most common (56%, 40%, and 39%, respectively), all of which are reported at an increased rate when comparing to the US Census. Self-reported ancestry results displayed similar patterns (p = 0.44). Autoimmune history was self-reported in 170 patients (13.6%), and family history of iSGS was present in 5.0%; neither varied based on ancestry. Twenty-four patients overall (1.9%) had predominantly non-Caucasian/non-European ancestry: 2.2% of the self-reported cohort and 1.3% of the testing service result cohort.

A cohort of primarily North American patients with iSGS report higher rates of ancestry from Northwestern Europe than the US population at large. These findings support potential genetic contributions to disease development. Additionally, as a subset of patients were identified as non-Caucasian within our cohort, further characterization of this "atypical" patient population should be performed to determine whether patients may be underdiagnosed worldwide.

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