Family History of OSA Contributes to Pathogenesis of the Condition

Jeremy Orr, MD

A new investigation found that family history was an important contributor to the pathogenesis of obstructive sleep apnea (OSA), and was responsible for much of its effect on mediated by loop gain and neck size.

The data was presented at the American Thoracic Society 2020 International Conference in San Francisco.

Previous research found that first-degree family history of OSA could be a potential risk factor for the sleep disorder, with estimates stating indicating ~40% of the variation in the apnea-hypopnea index (AHI).

However, the mechanisms of this effect have not been fully established.

As such, an investigative team led by Jeremy Orr, MD, Pulmonary and Critical Care Medicine at UC San Diego, tested the hypothesis regarding the effect of family history on AHI and how it is mediated through 1 or more known traits underlying OSA pathogenesis.

Orr and colleagues created a retrospective cohort based on a previous chart review of consecutive patients who were diagnosed with OSA (AHA≥5) based on an in-lab polysomnogram between January 2017 and December 2018. Each patients family history-status was explicitly noted.

The investigative team quantified 4 pathophysiological traits for each subject, including anatomical collapsibility, arousal threshold, loop gain, and pharyngeal dilator recruitment, which were determined via a validated polysomnography-based algorithm.

Following log-transforming of the AHI to increase normality, Orr and colleagues performed simple mediation analyses that included structural equation models. From there, the 4 traits and 2 proxy-markers of anatomical collapsibility functioned as candidate mediators, with age and sex being included as covariates.

A total of 355 patients with OSA were included in the study, all of whom had available data on family history of OSA and OSA traits. Among these patients, 104 (29%) has positive family history of OSA.

Investigators noted that both groups were similar in term of BMI, race and ethnicity. However, patients with a positive history of OSA tended to be younger compared to those without a positive history, with the median ages being 50 and 56, respectively.

Patients with a positive family history also tended to be female (50% versus 41%), and had more severe OSA based on a higher AHI (29 [17-60] vs 23 [12-50]).

Additionally, a positive family history was associated with a 37% (eβ=1.37) (P=0.001) higher AHI, partially mediated by loop gain (P>0.4). As such, this did not mediate its effect on the AHI.

In addition to confirming family history as an “important contributor” of OSA, the investigative team also believed this study suggested that high loop gain be considered as an endotype/phenotype for genome-wide association studies that focus on the genetic underpinnings of OSA.

“However, the majority of family history’s effect on AHI was not explained by traditional traits and markers of an unfavorable anatomy, and residual confounding or reverse causation cannot be excluded,” the team wrote.