A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2.
We conducted a genome-wide search for childhood obesity-associated traits, including BMI >/==" BORDER="0">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 >/==" BORDER="0">95th percentile. Among these 115 pedigrees, 97 had at least two sibs with a BMI >/==" BORDER="0">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.
Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8090, Institute of Biology of Lille, Pasteur Institute, Lille, France.
David
D
Meyre
Cécile
C
Lecoeur
Jérôme
J
Delplanque
Stephan
S
Francke
Vincent
V
Vatin
Emmanuelle
E
Durand
Jacques
J
Weill
Christian
C
Dina
Philippe
P
Froguel
D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005190:Family; D005602:France; D015894:Genome, Human; D006801:Humans; D007223:Infant; D009765:Obesity / Q000235:genetics*; D035781:Siblings; D018709:Statistics, Nonparametric