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Whole Genome Scan for Obstructive Sleep Apnea and Obesity in African-American Families

Western Australian Institute for Medical Research, Center for Medical Research, University of Western Australia, Perth, Australia; Department of Epidemiology and Biostatistics and Department of Pediatrics, Case Western Reserve University, and Rainbow Babies and Children's Hospital, Cleveland, Ohio; and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Lyle J. Palmer, Ph.D., Western Australian Institute for Medical Research, QE-II Medical Centre, B Block, Hospital Avenue, Nedlands 6009, Australia. E-mail: lyle{at}cyllene.uwa.edu.au

Obstructive sleep apnea (OSA) is a common, chronic disease associated with obesity. OSA and obesity are both prevalent in African Americans, who are also at increased risk for secondary complications. To identify susceptibility loci for OSA, we undertook a 9-centimorgans genome scan in 59 African-American pedigrees ascertained on the basis of either an affected individual with laboratory-confirmed disease or a proband who was a neighborhood control subject. Variance component linkage analysis was performed for the quantitative phenotypes apnea–hypopnea index (AHI) and body mass index. A candidate region on chromosome 8q (logarithm of odds [LOD] = 1.29, p = 0.006) gave the only evidence for linkage to the AHI. Body mass index was linked to multiple regions, most significantly to markers on chromosome 4q (LOD = 2.63, p = 0.0006) and 8q (LOD = 2.56, p = 0.0007). Evidence of linkage to the AHI was only slightly reduced after adjustment for body mass index. After adjustment for the AHI, some of the primary linkages to body mass index were greatly reduced whereas others remained suggestive. Our results suggest that there are both shared and unshared genetic factors underlying susceptibility to OSA and obesity, and that the genetic determinants of obesity in this population may be modulated by apnea severity.

Key Words: body mass index • genetic epidemiology • genome scan • obstructive sleep apnea • quantitative

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