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Department of Genetics, Southwest Foundation for Biomedical Research (A.G.C., L.J.M., J.B.), San Antonio, Texas 78245; Department of Internal Medicine and Molecular Science, University of Osaka Graduate School of Medicine (T.F., M.T., S.K., S.T., Y.M.), Osaka, Japan; Department of Medicine, TOPS Center for Obesity and Metabolic Research, and the Human and Molecular Genetics Center, Medical College of Wisconsin (G.S., H.J.J., A.E.K.B., D.M., A.K.), Milwaukee, Wisconsin 53226; and Center for Genomic Research, Genset (D.C.), Paris, France
Address all correspondence and requests for reprints to: Ahmed H. Kissebah, M.D., Ph.D., Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, Wisconsin 53226. E-mail: vdodge{at}mcw.edu
Abstract
Here we present the first genetic analysis of adiponectin levels, a newly identified adipocyte-derived protein. Recent work has suggested that adiponectin may play a role in mediating the effects of body weight as a risk factor for coronary artery disease. For this analysis we assayed serum levels of adiponectin in 1100 adults of predominantly northern European ancestry distributed across 170 families. Quantitative genetic analysis of adiponectin levels detected an additive genetic heritability of 46%. The maximum LOD score detected in a genome wide scan for adiponectin levels was 4.06 (P = 7.7 x 10-6), 35 cM from pter on chromosome 5. The second largest LOD score (LOD = 3.2; P = 6.2 x 10-5) was detected on chromosome 14, 29 cM from pter. The detection of a significant linkage with a quantitative trait locus on chromosome 5 provides strong evidence for a replication of a previously reported quantitative trait locus for obesity-related phenotypes. In addition, several secondary signals offer potential evidence of replications for additional previously reported obesity-related quantitative trait loci on chromosomes 2 and 10. Not only do these results identify quantitative trait loci with significant effects on a newly described, and potentially very important, adipocyte-derived protein, they also reveal the emergence of a consistent pattern of linkage results for obesity-related traits across a number of human populations.
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