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

Abstract

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.