Morgenthaler, Timothy I

ABSTRACT Obstructive sleep apnea (OSA) is a common, heritable disorder with diverse clinical presentations and etiologies. We conducted a genome-wide association meta-analysis of 492,107 individuals, including 46,028 OSA cases, identifying 14 genome-wide significant loci, eight of which are novel. Analyses adjusting for body mass index (BMI) revealed three loci independent of obesity, implicating alternative biological pathways contributing to disease. Integrative functional analyses, including chromatin interaction mapping, fine-mapping, and eQTL colocalization, prioritized candidate effector genes. Notably, implicated genes in chondrocytes were associated with craniofacial morphology in both mouse and human multivariate genotype-phenotype mapping, supporting a role for craniofacial structure in OSA risk. These findings highlight key genetic pathways (obesity-related, neurological, and craniofacial) underlying the development of OSA, offering new insights into its complex etiology.

Objectives/HypothesisMultiple system atrophy (MSA) is a degenerative neurologic disorder that can affect vocal fold mobility. Our aim was to further elucidate the impact of vocal fold motion impairment (VFMI) in MSA.Study DesignRetrospective case series.MethodsWe undertook a retrospective review of all MSA patients reporting voice or respiratory symptoms from 1975 to 2010 at Mayo Clinic Rochester who also received otolaryngologic examination.ResultsThirty‐eight MSA patients demonstrated VFMI. Median duration of vocal or respiratory symptoms prior to diagnosis of MSA was 12.0 months (range, 1–60 months). Stridor was present in 25 (68%) of patients. There was bilateral VFMI in 32 (82.4%) of the patients and isolated VFMI of the left true vocal fold (TVF) in six (17.6%) of the patients. No patients had isolated right VFMI. There was isolated unilateral or bilateral paresis in 21 (55.3%) of the patients and unilateral or bilateral complete paralysis in 15 (39.5%) of the patients. One patient presented with left TVF paralysis and right TVF paresis, whereas one other patient had findings of right TVF paralysis and left TVF paresis comprising the remaining 5.2% of patients with VFMI. The median survival after diagnosis of VFMI was 51.6 months. Unilateral or bilateral TVF paralysis was statistically associated with a decreased overall survival (P = .0384). The presence of stridor was not associated with adverse prognosis.ConclusionsThe increasing severity of VFMI negatively impacts overall survival in patients with MSA. Therefore, otolaryngologic examination is warranted at the time of MSA diagnosis.Level of Evidence4. Laryngoscope, 124:730–735, 2014