A Whole-Genome Scan for Obstructive Sleep Apnea and Obesity

• Published in: American journal of human genetics Vol. 72; no. 2; pp. 340 - 350
• Main Authors: Palmer, Lyle J., Buxbaum, Sarah G., Larkin, Emma, Patel, Sanjay R., Elston, Robert C., Tishler, Peter V., Redline, Susan
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.02.2003; University of Chicago Press; The American Society of Human Genetics
• Subjects: Adult; Aged; Biological and medical sciences; Body Mass Index; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 7; Cohort Studies; Female; Genetic Linkage; Genome, Human; Genotype; Humans; Lod Score; Longitudinal Studies; Male; Medical sciences; Metabolic diseases; Middle Aged; Obesity; Obesity - genetics; Pedigree; Phenotype; Sex Factors; Sleep Apnea, Obstructive - genetics; Human; Obesity; Nervous system diseases; Sleep apnea syndrome; Linkage; Respiratory disease; Pathogenesis; Nutrition disorder; Genotype; Genetic determinism; Obstruction; Respiratory tract; Genetics; Genome; Nutritional status
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/346064

Obstructive sleep apnea (OSA) is a common, chronic, complex disease associated with serious cardiovascular and neuropsychological sequelae and with substantial social and economic costs. Along with male gender, obesity is the most characteristic feature of OSA in adults. To identify susceptibility loci for OSA, we undertook a 9-cM genome scan in 66 white pedigrees ( n=349 subjects) ascertained on the basis of either an affected individual with laboratory-confirmed OSA or a proband who was a neighborhood control individual. Multipoint variance-component linkage analysis was performed for the OSA-associated quantitative phenotypes apnea-hypopnea index (AHI) and body mass index (BMI). Candidate regions on chromosomes 1p (LOD score 1.39), 2p (LOD score 1.64), 12p (LOD score 1.43), and 19p (LOD score 1.40) gave the most evidence for linkage to AHI. BMI was also linked to multiple regions, most significantly to markers on chromosomes 2p (LOD score 3.08), 7p (LOD score 2.53), and 12p (LOD score 3.41). Extended modeling indicated that the evidence for linkage to AHI was effectively removed after adjustment for BMI, with the exception of the candidate regions on chromosomes 2p (adjusted LOD score 1.33) and 19p (adjusted LOD score 1.45). After adjustment for AHI, the primary linkages to BMI remained suggestive but were roughly halved. Our results suggest that there are both shared and unshared genetic factors underlying susceptibility to OSA and obesity and that the interrelationship of OSA and obesity in white individuals may be partially explained by a common causal pathway involving one or more genes regulating both AHI and BMI levels.