The Familial Aggregation of Obstructive Sleep Apnea

Abstract An inherited basis for sleep-disordered breathing (SDB) has been suggested by reports of families with multiple affected members and by a previous study of the familial aggregation of symptoms of SDB. In this study, we quantify and characterize the aggregation of SDB and assess the degree to which familial similarities may be independent of obesity. This was a genetic-epidemiologic study that assessed the distribution of SDB in families identified through a proband with diagnosed sleep apnea and among families in the same community with no relative with known sleep apnea. SDB was assessed with overnight inhome monitoring of airflow, oxygen saturation, chest wall impedance, heart rate, and body movement. Standardized questionnaires were used to assess symptoms, and weight, height, and neck circumference were measured directly. Intergenerational and intragenerational correlation coefficients and pairwise odds ratios (ORs) were calculated with adjustment for proband sampling. In toto, 561 members of 91 families were studied: (1) 47 subjects with laboratory-confirmed SDB (index probands), (2) 44 community control subjects, and (3) the spouses and relatives of 1 and 2. Of all 91 families, 32 (35%) had two or more members with SDB, 30 (33%) had one affected member, and 29 had no affected members. SDB was more prevalent in the relatives of index probands (21%) than among neighborhood control subjects (12%) (p = 0.02). After adjusting for age, sex, race, and obesity, the odds of SDB, defined on the basis of age-specific threshold values for the respiratory disturbance index (RDI), was 1.3 greater in subjects with one affected relative, and 2.3 greater in subjects with three affected members when compared with subjects without affected family members. Intergenerational and intragenerational coefficients, describing the similarities in RDI levels among family members, were each 0.21 (p 0.005), and they were not reduced significantly with adjustment for obesity. These results suggest that SDB significantly aggregates within families and that risk increases progressively with increasing numbers of affected relatives. The familial aggregation of SDB is not explained entirely by familial similarities in body mass index (BMI) or neck circumference, suggesting the importance of other familial factors in increasing susceptibility to the disorder.