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Published ahead of print on April 7, 2004, doi:10.1164/rccm.200304-493OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 12, June 2004, 1314-1321

A more recent version of this article appeared on June 15, 2004
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Submitted on April 9, 2003
Accepted on April 2, 2004

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

Lyle J Palmer1*, Sarah G Buxbaum2, Emma K Larkin3, Sanjay R Patel4, Robert C Elston2, Peter V Tishler4, and Susan Redline3

1 Center for Medical Research, University of Western Australia, Western Australian Institute for Medical Research, Nedlands, Australia; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA, 2 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA, 3 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA; Department of Pediatrics, Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, OH, USA, 4 Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Channing Laboratory, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: lyle{at}cyllene.uwa.edu.au.

Obstructive sleep apnea is a common, chronic disease associated with obesity. Obstructive sleep apnea and obesity are both prevalent in African-Americans, who are also at increased risk for secondary complications. To identify susceptibility loci for obstructive sleep apnea, we undertook a 9cM 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. Variance component linkage analysis was performed for the quantitative phenotypes apnea-hypopnea index and body mass index. A candidate region on chromosome 8q (LOD=1.29, P=0.006) gave the only evidence for linkage to apnea-hypopnea index. 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). The evidence for linkage to apnea-hypopnea index was only slightly reduced after adjustment for body mass index. After adjustment for the apnea-hypopnea index, some of the primary linkages to body mass index were greatly reduced while others remained suggestive. Our results suggest that there are both shared and unshared genetic factors underlying susceptibility to obstructive sleep apnea and obesity, and that the genetic determinants of obesity in this population may be modulated by apnea severity.
Key words: genome scan, obstructive sleep apnea, genetic epidemiology, quantitative, BMI




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