The Genetic Basis of Plasma Variation in Adiponectin, a Global Endophenotype for Obesity and the Metabolic Syndrome
Anthony G. Comuzzie,
Tohru Funahashi,
Gabriele Sonnenberg,
Lisa J. Martin,
Howard J. Jacob,
Anne E. Kwitek Black,
Diana Maas,
Masahiko Takahashi,
Shinji Kihara,
Sachiyo Tanaka,
Yuji Matsuzawa,
John Blangero,
Daniel Cohen and
Ahmed Kissebah
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 hassuggested
that adiponectin may play a role in mediating theeffects of body
weight as a risk factor for coronary arterydisease. For this analysis
we assayed serum levels of adiponectinin 1100 adults of predominantly
northern European ancestry distributedacross 170 families.
Quantitative genetic analysis of adiponectinlevels detected an
additive genetic heritability of 46%. Themaximum LOD score detected
in a genome wide scan for adiponectinlevels was 4.06
(P = 7.7 x 10-6), 35 cM from
pter on chromosome5. The second largest LOD score (LOD = 3.2;
P = 6.2 x 10-5)was detected on
chromosome 14, 29 cM from pter. The detectionof a significant linkage
with a quantitative trait locus onchromosome 5 provides strong
evidence for a replication of apreviously reported quantitative trait
locus for obesity-relatedphenotypes. In addition, several secondary
signals offer potentialevidence of replications for additional
previously reportedobesity-related quantitative trait loci on
chromosomes 2 and10. Not only do these results identify quantitative
trait lociwith significant effects on a newly described, and
potentiallyvery important, adipocyte-derived protein, they also reveal
theemergence of a consistent pattern of linkage results for
obesity-relatedtraits across a number of human populations.
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