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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 3 1199-1205
Copyright © 2001 by The Endocrine Society

Original Studies

Genome-Wide Scan of Obesity in the Old Order Amish1

Wen-Chi Hsueh, Braxton D. Mitchell, Jennifer L. Schneider, Pamela L. St. Jean, Toni I. Pollin, Margaret G. Ehm, Michael J. Wagner, Daniel K. Burns, Hakan Sakul2, Callum J. Bell3 and Alan R. Shuldiner

Southwest Foundation for Biomedical Research (W.-C.H., B.D.M., J.L.S.), San Antonio, Texas 78245; GlaxoWellcome, Inc. (P.L.S.J., M.G.E., M.J.W., D.K.B.), Research Triangle Park, North Carolina 27709; University of Maryland School of Medicine (T.I.P., A.R.S.), Baltimore, Maryland 21201; and Axys Pharmaceuticals (H.S., C.J.B.), La Jolla, California 92037

Address all correspondence and requests for reprints to: Dr. Braxton D. Mitchell, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, 725 West Lombard Street, Room S-420, Baltimore, Maryland 21201. E-mail: bmitchel{at}medicine.umaryland.edu

To identify the genetic determinants of typical obesity, we performed a genome-wide scan of obesity-related traits using data from the Amish. Multipoint linkage analysis was performed using a variance components procedure on body mass index (BMI), waist circumference, percentage of body fat, and serum leptin concentrations. All 672 individuals were genotyped for 357 markers in 22 autosomes. We observed modest evidence for linkage, with the maximum log odds (lod) scores for linkage for these traits occurring on chromosomes 3p (percentage of body fat: lod = 1.61, near the peroxisome proliferator-activated receptor-{alpha} gene), 14q (waist: lod = 1.80), and 16p (leptin: lod = 1.72; BMI: lod = 1.68). We also tested for linkage to BMI-adjusted leptin concentrations and observed suggestive evidence for linkage on chromosome 10p (lod = 2.73), approximately 10–20 cM telomeric from obesity loci previously reported in French and German Caucasians. Two additional linkage signals for this trait were observed on chromosomes 7q (lod = 1.77, ~20 cM from the leptin gene) and 14q (lod = 2.47). Follow-up studies may be warranted to pursue some of these linkage signals, especially those detected near known obesity candidate genes, and those in regions coinciding with linkage signals reported previously.




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