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Diabetes 53:803-811, 2004
© 2004 by the American Diabetes Association, Inc.

A Genome-Wide Scan for Childhood Obesity–Associated Traits in French Families Shows Significant Linkage on Chromosome 6q22.31-q23.2

David Meyre1, Cécile Lecoeur2, Jérôme Delplanque1, Stephan Francke1, Vincent Vatin1, Emmanuelle Durand1, Jacques Weill1,3, Christian Dina1, and Philippe Froguel1,2

1 Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8090, Institute of Biology of Lille, Pasteur Institute, Lille, France
2 Hammersmith Genome Centre and Genomic Medicine, Imperial College, London, U.K
3 Department of Pediatrics, Jeanne de Flandres Hospital, Lille, France

We conducted a genome-wide search for childhood obesity–associated traits, including BMI >=95th percentile (PCT95), 97th percentile (PCT97), and 99th percentile (PCT99) as well as age of adiposity rebound (AAR), which corresponds to the beginning of the second rise in childhood adiposity. A set of 431 microsatellite markers was genotyped in 506 subjects from 115 multiplex French Caucasian families, with at least one child with a BMI >=95th percentile. Among these 115 pedigrees, 97 had at least two sibs with a BMI >=95th percentile. Fine-mapping was performed in the seven most positive loci. Nonparametric multipoint analyses revealed six regions of significant or suggestive linkage on chromosomes 2q33.2-q36.3, 6q22.31-q23.2, and 17p13 for PCT95, PCT97, or PCT99 and 15q12-q15.1, 16q22.1-q24.1, and 19p13.3-p13.11 for AAR. The strongest evidence of linkage was detected on chromosome 6q22.31 for PCT97 (maximum likelihood score: 4.06) at the marker D6S287. This logarithm of odds score meets genome-wide significance tested through simulation (empirical genome-wide P = 0.01 [0.0027–0.0254]). Six independent ge-nome scans in adults have reported quantitative trait loci on 6q linked to energy or glucose homeostasis-associated phenotypes. Possible candidate genes in this region include SIM1, MCHR2, and PC-1.

Address correspondence and reprint requests to Philippe Froguel, CNRS UMR 8090, Institute of Biology, Institute Pasteur of Lille, 1, rue du Pr. Calmette, B.P.447 59021 Lille Cedex, France. E-mail: froguel{at}mail-good.pasteur-lille.fr


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.