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Family Aggregation of Upper Airway Soft Tissue Structures in Normal Subjects and Patients with Sleep Apnea

Center for Sleep and Respiratory Neurobiology; Pulmonary, Allergy, and Critical Care Division; and Division of Sleep Medicine, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania

Correspondence and requests for reprints should be addressed to Richard J. Schwab, M.D., Center for Sleep and Respiratory Neurobiology, 893 Maloney Building, University of Pennsylvania Medical Center, 3600 Spruce Street, Philadelphia, PA 19104-4283. E-mail: rschwab{at}mail.med.upenn.edu

Rationale: Sleep apnea is believed to be a genetic disorder. Thus, we hypothesized that anatomic risk factors for sleep apnea would demonstrate family aggregation.

Objectives: We used volumetric magnetic resonance imaging in a sib pair "quad" design to study the family aggregation of the size of upper airway soft tissue structures that are associated with increased risk for obstructive sleep apnea.

Methods: We examined 55 sleep apnea probands (apnea–hypopnea index [AHI]: 43.2 ± 26.3 events/h), 55 proband siblings (AHI: 11.8 ± 16.6 events/h), 55 control subjects (AHI: 2.1 ± 1.7 events/h), and 55 control siblings (AHI: 4.2 ± 4.0 events/h). The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for visceral neck fat and craniofacial dimensions.

Measurements and Main Results: The data support our a priori hypothesis that the volume of the important upper airway soft tissue structures is heritable. The volume of the lateral pharyngeal walls (h² = 36.8%; p = 0.001), tongue (h² = 36.5%; p = 0.0001), and total soft tissue (h² = 37.5%; p = 0.0001) demonstrated significant levels of heritability after adjusting for sex, ethnicity, age, visceral neck fat, and craniofacial dimensions. In addition, our data indicate that heritability of the upper airway soft tissue structures is found in normal subjects and patients with apnea. Thus, it is not simply a consequence of the prevalence of apnea.

Conclusions: This is the first time family aggregation of size of the upper airway soft tissue structures has been demonstrated.

Key Words: family aggregation • genetics • magnetic resonance imaging • obstructive sleep apnea • upper airway

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